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D. Morgensztern
Moderator of
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MINI 29 - Meta Analyses and Trial Conduct (ID 156)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 15
- Moderators:D. Morgensztern, M. Redman
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 2a-3b
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MINI29.01 - Squamous Cell Carcinoma of Lung in the United States: Analysis of the National Cancer Database (NCDB) (ID 2747)
18:30 - 18:35 | Author(s): M. Behera, T.K. Owonikoko, Y. Liu, T.W. Gillespie, M. Yuan, R.N. Pillai, C. Steuer, K.A. Higgins, S. Pakkala, C.P. Belani, F. Khuri, S.S. Ramalingam
- Abstract
Background:
Lung squamous cell carcinoma (SCC) is the second most common histological sub type of lung cancer and accounts for about 30% of all non-small cell lung cancers (NSCLC). We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the epidemiology, patterns of care, outcomes and temporal changes in incidence of SCC.
Methods:
The NCDB was queried from 1998 to 2011 for SCC using ICD-O-3 codes. Temporal changes in incidence were estimated in intervals (1998-1999, 2000-2003, 2004-2007, 2008-2011). The univariate association with covariates between SCC and other subtypes of NSCLC was assessed using Chi-square test or ANOVA. The univariate (UV) and multivariable analysis (MV) with OS were conducted by Cox proportional hazards model and log-rank tests. All statistical analyses were conducted using SAS Version 9.3.
Results:
A total of 435,358 pts with SCC were included in the analysis and accounted for 28% of all NSCLC pts in NCDB. Pt characteristics: median age 70 (18-90 yrs); males 64%; whites 87%; academic centers 27%; metro locations 78%; government insured 72%; Charlson/Deyo comorbidity score (CDS) 0 in 55% and ≥2 in 15%, and stage III/IV- 34/31%. Chemotherapy was used in 39% of pts, radiation in 46% and surgery in 32%. Approximately 19% of the pts did not receive any of the three treatments. Incidence of SCC decreased over time (35%, 28%, 26%, 27%) vs. increasing trend in non-SCC (65%, 72%, 75%, 72%); p<0.001). The trend was similar across all races and sex. SCC was associated with a higher co-comorbidity burden than non-SCC across all stages (CDS 0: 55% vs. 62%; CDS 1: 31% vs. 27%; CDS ≥2: 15% vs. 11%; p<0.001). SCC was associated with inferior 5 yr survival vs. non-SCC in all stages (stage I- 30% vs. 41%, stage II- 16% vs. 21%, stage III- 8.5% vs.10%, stage IV- 1.9% vs. 2.5% respectively; p<0.0001). The 1 yr survival in stage IV SCC is 19.6% vs. 22.2% in non-SCC (p<0.0001). Males had worse survival (HR 1.11 (1.09-1.13; p<0.001). Pts at community centers had worse survival vs. academic centers (HR 1.27 (1.23-1.30; p<0.001). An increasing trend in chemotherapy use was observed (31% in 1998 to 43% in 2011) vs. a decreasing trend in use of radiation (52% in 1998 to 46% in 2011) and surgery (32% in 1998 to 27% in 2011). Chemotherapy was received by 48% of patients with stage IV SCC. Chemotherapy use across other stages: 0/I- 18%, II- 46%, III- 60%. Males were more likely to receive any treatment (OR 1.12 (1.08-1.15); p<0.001). Pts that received any treatment had significantly better 5 year survival than those who did not receive any (20.3% vs. 3.3%, p<0.0001)
Conclusion:
SCC accounted for 28% of all cases of NSCLC in the United States, was associated with higher comorbidities and a significantly worse survival compared to non-SCC of the lung. Chemotherapy was used in only 48% of pts with stage IV SCC.
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MINI29.02 - Effect of Statins and Metformin on Survival in Patients with Non-Small Cell Lung Cancer (ID 363)
18:35 - 18:40 | Author(s): N. Duma, M. Kang, K. Abu-Ihweij, M. Choudhary, A. Gandhi, M. Gutierrez
- Abstract
- Presentation
Background:
Lung cancer is the number one cause of cancer-related death worldwide; with the incidence of non-small cell lung cancer (NSCLC) risen dramatically, the importance of understanding the influence of comorbidities and their treatments takes a great importance. The aim of this study was to investigate the effect of statins and metformin on survival in patients with NSCLC.
Methods:
We reviewed the records of all patients diagnosed with NSCLC at our institution from 2011 to 2013. Demographics, tumor characteristics, comorbidities, statin/ metformin use and survival were analyzed. Cox regression was used for multivariate analysis.
Results:
A total 205 patients were studied. Median age at diagnosis was 65 years (40-91), there were more males than females (56% vs. 44%, p<0.01. 74% (152) were current or former smokers with average 40 pack years (5-60). The Median BMI was 26.5kg/m2 (18-44), ECOG status was 1 (0-4) and serum creatinine of 1.0 (0.4-3.5). Regarding comorbidities: 48% (98) had hypertension, 45% (93) hyperlipidemia, 22% (44) COPD and 19% (39) diabetes mellitus. At diagnosis, 66% (136) of the patients had stage III/IV disease vs. 25% (69) with stage I/II, p<0.0001. Adenocarcinoma was the most common histologic subtype (61%), followed by squamous cell carcinoma (27%). 42% received surgery, 80% systemic chemotherapy and 32% radiation. Median survival was 1520 days (95% CI: 1310-1765). 42% (87) of the patients were taking statins and 13% (27) metformin. About the statin use, 58% of the patients were using statins for 25-48 months, 12% for >48 months, 11% for 13-24 months and 18% for less than 12 months. Female gender (OR: 1.98, p<0.001), age<65 years (OR: 0.89, p<0.01) and statin use (OR: 0.78, p<0.02) were independent predictors of survival by multivariate analysis. Metformin use was not a predictor of survival by univariate or multivariate analysis in this group of patients.
Conclusion:
In our cohort, we observed that almost half of the patients had hypertension and hyperlipidemia with statin use been a significant predictor of survival. Statins are one of the mostly widely prescribed drugs in the US; their proven anti-inflammatory effects may play a role in inhibiting cancer growth. However, the exact mechanisms by which statins inhibit cancer proliferation remains unclear. While other observational studies have looked at statins and risk of developing cancer, we specifically looked at the effect of statins on survival in patients on statin therapy prior to cancer diagnosis. More studies are needed to enhance our understanding of the effect of statins on lung cancer.
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MINI29.03 - Prognostic Value of Biomarkers Associated with Glucose Metabolism and Systemic Inflammation in Advanced On-Small Cell Lung Cancer (NSCLC) (ID 3061)
18:40 - 18:45 | Author(s): M.J. Fidler, G.C. Lobato, S. Kerns, S. Basu, C.L. Fhied, R. Pithadia, I. Tarhoni, M. Batus, P. Bonomi, J.A. Borgia
- Abstract
- Presentation
Background:
Alterations in glucose metabolism and appetite stimulating hormones have been correlated with inflammation but there is little information on frequency and prognosis in newly diagnosed stage IV non-small cell lung cancer (NSCLC) This study objective was to identify associations of circulating biomarkers of glucose metabolism and inflammation with prognosis in pre-treatment sera from stage IV NSCLC patients selected for platinum doublet based chemotherapy.
Methods:
Pretreatment serum from 118 Pts with frontline stage IV NSCLC were evaluated with the Bio-Plex Pro Human Diabetes Assay panel (adiponectin, adipsin, c-peptide, ghrelin, gastrin inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, IL-6, insulin, leptin, Plasminogen activator inhibitor-1, resistin, TNFα, vistatin) and HSTCMAG-28SK | MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay (Fractalkin, GM-CSF, IFNγ, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, IL-21, IL-23, ITAC, macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-3α, TNFα) on a FlexMAP 3D system (Luminex Corp.). Pts were treated with standard platinum doublets based chemotherapy. Associations of biomarkers with progression free and overall survival (PFS,OS) outcomes were assessed using multivariate Cox PH analyses.
Results:
Most patients had metabolic levels below the prognostic threshold. However, high levels of insulin, GIP, glucagon, visfatin, ghrelin, GLP-1 were significantly associated (p<0.05) with shorter PFS. Low levels of adipisin (deficiency of which is associated with obesity) was associated with shorter PFS (p=.0185). High levels of pro-inflammatory markers: ITAC, GM-CSF, Fratalkine, INF-ϒ, IL-12p70, IL-13, IL17A, IL-4, IL-23, IL8.4, MIP-α, MIP-1 were also associated with poor PFS (p<0.05) (See Table I for more details on select biomarkers) High levels of these endocrine markers (except insulin and GIP) were associated with shorter OS as were ITAC, GMCSF, IL12p70, IL-13, IL4, IL23, IL5 (p<0.05). Table I. Biomarker correlation with progression free survivalMarker Cutoff-pg/mL N < N > Median PFS < Median PFS> Logrank p Insulin 1004.9 82 36 6.08 4.04 0.026161 Glucagon 361.2 110 8 5.46 1.71 0.010219 Visfatin 8298.3 109 9 5.65 1.45 8.77E-06 Ghrelin 2897.2 104 14 6.02 2.12 0.009423 GLP.1 268.8 109 9 5.65 1.97 0.000618 ITAC 104.7 99 19 5.82 2.96 0.012529 Fractalkine 271.7 97 21 6.08 3.16 0.0067 IL.12.p70. 17.0 109 9 5.65 3.16 0.010631 IL.13 14.9 105 13 5.82 2.76 0.001533 IL.17A 49.4 102 16 5.82 3.65 0.004862 IL.4 66.1 104 14 6.02 2.96 0.000917 IL.8.4 3.0 25 93 12.8 4.8 0.008985
Conclusion:
Imbalances in the glucose metabolism pathway and increased levels of pro-inflammatory circulating markers were uncommon but consistently associated with a poor prognosis in stage IV NSCLC patients early in their treatment cycle. Alterations in these systems have been associated with cancer cachexia and may be targets for intervention in improving prognosis for select patients with NSCLC.
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MINI29.04 - The Use of Metformin and Proper Glycemic Control Are Associated with Improved Survival in Non-Small Cell Lung Cancer Patients (ID 1612)
18:45 - 18:50 | Author(s): O. Arrieta Rodriguez, E. Varela-Santoyo, E. Soto-Pérez-De-Celis, R. Sánchez-Reyes, M. De La Torre-Vallejo, A.F. Cardona
- Abstract
- Presentation
Background:
Previous population-based studies have shown an association between metformin use and improved survival among diabetic patients with lung cancer. We sought to analyze the effect of diabetes and its treatment in terms of survival in Mexican patients with lung cancer treated at a single institution
Methods:
1106 patients were included. Outcomes were compared between patients with (n=186) and without diabetes (n=920). Characteristics associated with antidiabetic treatment and with proper glycemic control (defined as mean plasma glucose <130mg/dL) were examined. Overall survival (OS) among the different patient populations was analyzed using Kaplan-Meier curves and multivariate analysis was used to determine the influence of patient and tumor characteristics on survival
Results:
OS for the entire population was 18.3 months (95% CI 16.1-20.4). There was no difference in OS between diabetic and non-diabetic patients (18.5 vs 16.4 months, p = 0.62). Diabetic patients taking metformin had a superior OS than those taking other antidiabetic treatment (25.6 vs 13.2 months, p = 0.001), and those with proper glycemic control had a better OS than those without proper glycemic control (40.5 vs 13.2 months, p<0.001). Both the use of metformin (HR 0.57 p = 0.017) and proper glycemic control (HR 0.40, p =0.002) were significant protective factors in the diabetic patient population.
Conclusion:
Proper glycemic control and metformin use have a beneficial effect on the survival of patients with diabetes and lung cancer. Studies using metformin in lung cancer should include measures of proper glycemic control as fundamental variables.
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MINI29.05 - Discussant for MINI29.01, MINI29.02, MINI29.03, MINI29.04 (ID 3385)
18:50 - 19:00 | Author(s): D.J. Stewart
- Abstract
- Presentation
Abstract not provided
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MINI29.06 - Are Clinical Trial Eligibility Criteria an Accurate Reflection of a Real World Population of Advanced Lung Cancer Patients? (ID 1398)
19:00 - 19:05 | Author(s): K. Al-Baimani, H. Jonker, T. Zhang, G. Goss, S.A. Laurie, G. Nicholas, P. Wheatley-Price
- Abstract
- Presentation
Background:
Modern systemic treatment options for advanced NSCLC have largely been established from clinical trials (CTs). It is estimated that less than 10% of cancer patients enter a CT, but this subgroup drives oncology practice and impacts treatment decisions for other cancer patients. The advantage of CTs comes from solid internal validity and stringent methodology. Nonetheless, the generalizability of CTs could be questioned due to the high selectivity of eligibility criteria. We investigated clinical trial eligibility in an unselected NSCLC population
Methods:
With ethics approval, a retrospective chart review was performed of patients with de novo advanced NSCLC assessed by medical oncologists at a large academic cancer centre, serving a mixed urban and rural population, between September 2009 and September 2012. Data collected included patient demographics, stage, performance status, histology, treatment details and outcome. Two sets (A and B) of arbitrary eligibility criteria were created using common criteria from phase 3 CTs. These criteria were applied to this cohort to identify the proportions of patient who would hypothetically qualify for CT enrollment. Criteria A required: ECOG 0 or 1, absence of brain metastases, Creatinine < 120 and the absence of second malignancy. Criteria B, allowing broader inclusion, only required ECOG 0-2 and Creatinine < 120. We investigated survival among eligible/ineligible and treated/untreated patients.
Results:
528 patients were included: 55% male; 50% ECOG 0-1; 58% adenocarcinoma, 22% squamous cell; 7% stage IIIB and 93% stage IV. Using the strict CT criteria (A), only 144 (27%) patients were considered eligible. Of those, 79% actually received systemic therapy. From 384 patients who would have been ineligible for the CT, 178 patients (46%) still received systemic therapy. There was a trend to longer median overall survival (mOS) in the eligible treated compared to eligible non-treated patients (11.6 vs 8.1 months p=0.12). mOS was significantly longer in the non-treated eligible cohort compared to the non-treated ineligible cohort (8.1 vs 3.8 months p=0.003). The eligible treated and non-eligible treated had similar mOS ( 11.6 vs 10.2 months, p= 0.10). When less strict eligibility criteria (B) were applied, 343 patients (65%) would have been eligible, of whom 240 patients (70%) actually received systemic therapy. From the remaining ineligible 185 patients, only 51 (28%) received treatment. The mOS was similar in the treated patient whether eligible or ineligible (10.9 vs 10.1 months, p=0.57). As seen in criteria A, significantly longer mOS was observed in the eligible untreated compared to the ineligible untreated ( 4.9 vs 3.5 months p<0.001).
Conclusion:
While clinical trial criteria restrict study entry to the fittest patients, these results suggest that they do not reflect the broader patient population, as many ‘ineligible’ patients received therapy. Extrapolation of treatment paradigms to non-trial eligible populations is common, and may be reasonable based on these results. We observed similar survival among treated patients, whether trial eligible or not. This suggests that clinical judgement is more important than trial eligibility. In order to broaden trial participation, we could hypothesize that trial eligibility criteria could be relaxed.
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MINI29.07 - CNS Disease Enrollment Criteria for NSCLC Drug Trials (ID 908)
19:05 - 19:10 | Author(s): E.M. Berge, C.E. McCoach, X. Lu, A.E. Barón, R. Camidge
- Abstract
- Presentation
Background:
CNS metastases are common in NSCLC, yet clinical trials of new drugs in NSCLC have widely varying inclusion and exclusion criteria in relation to CNS disease. CNS disease that has received local therapy may be dormant, confounding any subsequent drug benefit, whereas untreated CNS disease may reduce PFS if CNS and systemic drug exposure differs. Recently, RANO guidelines propose explicitly explored activity in CNS disease within solid tumor drug trials. The true extent of variation in CNS related enrollment criteria in NSCLC clinical trials has not been documented before.
Methods:
ClinicalTrials.gov was interrogated on September 11, 2014 looking for interventional drug trials including advanced NSCLC. The following characteristics were extracted: 1) trial phase; 2) experimental arm therapy (chemotherapy, targeted therapy, immunotherapy, anti-angiogenic); 3) location (US, International only, US + International); 4) sponsor (Industry, University/IIT, Cooperative Group, NCI); 5) CNS disease allowance (strict exclusion, allowed after local treatment (surgery/radiation), unrestricted/untreated disease allowed). Industry sponsorship was divided into ‘large pharmaceutical’, (top decile by number of sponsored trials) and ‘small pharmaceutical’ (lower 9 deciles). Exclusion of CNS metastasis was treated as a binary variable and grouped as ‘strict exclusion’ vs. ‘allowed CNS metastasis’ (‘allowed with treatment’ and ‘allowed untreated’). Univariable and multivariable logistic regression models were fit to test the association between exclusion of CNS metastasis and trial characteristics. Statistical significance was set at 0.05 with no adjustment for multiple testing.
Results:
Of 735 trials involving NSCLC, 325 (44%) were excluded from analysis mostly because of allowance of early stage NSCLC (50%, n=164), or no active therapy inclusion (45%, n=146). In the remaining 406 trials, patients with CNS metastases were excluded in 58 (14%), allowed after local treatment in 165 (41%), and allowed with no prior treatment in 104 (26%). CNS criteria were not referenced in the available information in 79 (19%) trials which were excluded from further analysis. On univariable analysis, the odds of CNS metastasis exclusion on trial were significantly lower in trials with vs. without targeted therapy (OR 0.44, 95% CI: 0.25-0.78, p=0.005) and significantly higher in trials with vs. without immunotherapy (OR 2.13, 95% CI: 1.06-4.28, p=0.04). No other univariable associations were significant. In multivariable analysis, after adjustment for all other factors, only trials located at international only vs. US only sites had greater odds of exclusion of CNS metastasis (OR 1.64, 95% CI 0.84-3.22; p=0.03).
Conclusion:
Although univariable analysis suggests class of agent may influence trial design, in multivariable analysis trial location was the only variable associated with strict exclusion of CNS metastases. This raises the possibility of exclusion based on historical/cultural rather than scientific factors. With 18% of trials (58/327) excluding all CNS disease and 50% (165/327) only allowing CNS disease if previously treated, less than a third of NSCLC trials permit unequivocal assessment of CNS activity (104/327). Given the high frequency of CNS disease in NSCLC, sponsors should consider consciously tailoring trial designs to more explicitly explore efficacy in this patient population.
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MINI29.08 - Innovation in Non-Small Cell Lung Cancer (NSCLC): Where Are the Clinically Meaningful Outcomes? (ID 1280)
19:10 - 19:15 | Author(s): L.M. Hess, S.L. Able, G.C. Carter, J.A. Treat
- Abstract
- Presentation
Background:
The American Society of Clinical Oncology (ASCO) recently developed a set of recommended targets for clinically meaningful outcomes to encourage patients, advocates and investigators to expect more of clinical trials in the future and to encourage investigators to design trials and select agents that have the most promise. A systematic literature review was conducted to identify where and how research has successfully met the bar for meaningful improvements in NSCLC patient survival.
Methods:
A systematic search strategy was implemented in MedLine and EMBASE to identify randomized phase III trials reporting overall survival (OS) outcomes from 1974-present. Eligible studies were those that reported OS data in terms of a hazard ratio (HR) or median OS. Patients in the eligible randomized trials were NSCLC patients treated in the first (1L) or post-first line (2L+) setting. Data were extracted related to study population, histology, interventions, and survival from trials of patients with advanced or metastatic disease. All eligibility determinations and extracted data were reviewed by two researchers for accuracy.
Results:
The search strategy identified 2051 articles that were reviewed for eligibility. Of these, 245 were eligible for inclusion. 198 (80.8%) studied 1L, 45 (18.4%) 2L+, and 2 investigated both lines. Of all articles, 51 (20.8%) found significant improvement in survival (Figure 1). Of these, 45 (88.2%) were 1L (41 studies). 14/41 (34.1%) were terminated early or had major protocol changes during study enrollment, and 5/41 (12.2%) reported inconsistent outcomes. In significant 1L studies, the median OS improvement ranged from 0.3-7.0m and HRs ranged from 0.35 to 0.87. The 4 2L+ positive studies, OS improvement ranged from 1.4-2.8m and HRs from 0.70-0.86. Of all 198 1L publications, 12 studies met the significant HR <0.80 bar and an additional 12 studies reported statistically significant gains of ≥2.5m OS. Figure 1. Publications reporting significant improvement in survival Figure 1
Conclusion:
There is a need to improve survival outcomes for patients in NSCLC. In 1L, few studies would have met the ASCO target. Only four 2L+ trials were identified with significant improvements in NSCLC. The results of this systematic literature review inform the interpretation of research and the new bar recommended for meaningful outcomes.
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MINI29.09 - Recommendations for Standardized Efficacy Data Specifications in Lung Cancer (ID 1599)
19:15 - 19:20 | Author(s): S. Khozin, G. Blumenthal, A. Khomyanina, B. Brodsky, R. Fitzmartin, P. Keegan, R. Pazdur
- Abstract
- Presentation
Background:
There are general standards for common clinical trial data elements submitted to US Food and Drug Administration (FDA) in a new drug application (NDA) or biologic license agreement (BLA). There is, however, considerable heterogeneity in the structure of data elements that are unique to a particular therapeutic area. As part of an effort organized by Coalition for Accelerating Standards and Therapies (CFAST), we developed specifications for efficacy data standardization in lung cancer.
Methods:
Using FDA guidance documents, NDA and BLA reviews, sample case report forms, and clinical trial datasets, we identified data elements in lung cancer clinical trials that are essential in evaluating the efficacy of new drugs and biologics. We constructed a concept map outlining the data elements and specifying their relational structure.
Results:
Data elements were captured under two main categories: efficacy endpoints (Figure 1) and covariates (Figure 2). Efficacy endpoints consist of overall survival, progression-free survival, objective response rate, duration of response, and disease-free survival. All lesions are assigned an organ-specific code. Data on tumor kinetics are captured as continuous variables supporting precise estimation of response while capturing all the requirements of Response Evaluation Criteria in Solid Tumors, version 1.1. Covariates were divided into disease and patient characteristics. Disease characteristics include specifications on molecular, immunohistochemical, and histological classification of tumors and detailed staging variables. Molecular definitions follow established nomenclature and include information on mutation subtypes as indicated. Patient characteristics include information on prior therapy, race and ethnicity. Figure 1 Figure 2
Conclusion:
The data elements we have identified (Figures 1 and 2) include concepts not adequately captured in current data standards and highlight important regulatory needs for the efficacy evaluation of new drugs and biologics in lung cancer. These specifications will be integrated with CFAST’s efforts to promote the development of lung cancer-specific data standards.
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MINI29.10 - Discussant for MINI29.06, MINI29.07, MINI29.08 (ID 3386)
19:20 - 19:30 | Author(s): M. Redman
- Abstract
- Presentation
Abstract not provided
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MINI29.11 - Assessing Patient-Reported Symptoms in Non-Small Cell Lung Cancer Clinical Trials (ID 2195)
19:30 - 19:35 | Author(s): A.K. Campbell, M. Martin, J. Lungershausen, J.M. Arduino, T.M. Atkinson, J..K. McCarrier, S.J. Coons, A. Liepa
- Abstract
- Presentation
Background:
In collaboration with the FDA, the Patient-Reported Outcome (PRO) Consortium’s Non-Small Cell Lung Cancer (NSCLC) Working Group (WG) has completed the initial development of a new PRO measure to assess symptom-related treatment benefit in clinical trials of advanced NSCLC to support labeling claims.
Methods:
Symptoms relevant to NSCLC patients were identified from the literature. This was followed by concept elicitation interviews conducted with patients at six US sites. Interview transcripts were coded using Atlas.ti software and concepts were grouped by similar content and subsequently reviewed by the NSCLC WG members and an expert panel in order to identify the symptoms most relevant for assessing treatment benefit. Preliminary items were generated and combined into a draft measure for cognitive testing with NSCLC patients for both item refinement and for assessing measurement equivalence between the original paper format and an electronic PRO (ePRO) data collection format (i.e., tablet).
Results:
For concept elicitation, the 51 patients interviewed had a mean age of 64.9 years [range 46-86], 51% were female, and 75% were white (non-Hispanic). Current NSCLC staging was: Stage I (12%), III (37%), and IV (51%). A total of 19 (37%) were treatment-naïve, 18 (35%) had received first-line treatment only, and 14 (27%) had received second- or third-line treatment. The most commonly expressed symptom was fatigue, described by patients as tiredness, lack of energy, tiring easily, and weakness. Other symptom concepts expressed included general pain, chest pain, cough, shortness of breath, difficulty breathing, appetite change, and coughing up blood. Items were drafted to assess either symptom frequency or severity for nine distinct symptoms using a 7-day recall period. Cognitive interviews were conducted in 3 waves to support iterative refinement. 20 additional NSCLC patients participated [mean age 65.2 years (range 44-83); 40% female; 75% white (non-Hispanic); 50% Stage III and 50% Stage IV]. During cognitive interviews, an 11-point numeric rating scale (NRS) and a 5-point verbal rating scale (VRS) were tested. Results indicated the 5-point VRS was better understood than the 11-point NRS. Further item refinement resulted in a 7-item measure covering pain (2 items: pain in chest, pain elsewhere), cough, shortness of breath, fatigue (2 items: energy, tiredness), and appetite. Patients reported no differences between tablet and paper data collection formats in regard to how they would interpret and respond to the items.
Conclusion:
NSCLC symptoms elicited from patients, across varied disease stages and treatments, were concordant with the pathophysiology of NSCLC. A new symptom-based PRO measure is being developed in accordance with the FDA’s PRO Guidance. The content is supported by existing literature, patient-reported experiences, and expert opinion. The draft measure (i.e., Non-Small Cell Lung Cancer Symptom Assessment Questionnaire [NSCLC-SAQ]) has been programmed onto an ePRO tablet for quantitative testing. Once complete, the NSCLC-SAQ and supporting evidence will be submitted to the FDA for its qualification as an efficacy endpoint measure to quantify treatment benefit for product evaluation and labeling.
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MINI29.12 - Patients with Advanced Non-Small Cell Lung Cancer: Are Research Biopsies a Barrier to Participation in Clinical Trials? (ID 663)
19:35 - 19:40 | Author(s): C. Lim, M. Sung, N. Nouriany, M. Sawczak, T. Paul, N. Perera-Low, A. Foster, D. Zawisza, R. Feld, G. Liu, F. Shepherd, N. Leighl
- Abstract
- Presentation
Background:
The evolution of targeted therapy in non-small cell lung cancer (NSCLC) has led to growing complexity of clinical research and a heightened expectation of clinical benefit for participants. Clinical trials in NSCLC increasingly require mandatory tumour samples or research biopsies, both potential barriers for trial participation. We assessed the impact of performing research biopsies in advanced NSCLC on clinical trial enrollment.
Methods:
We conducted a retrospective chart review of patients with advanced NSCLC evaluated for systemic therapy clinical trials at the Princess Margaret Cancer Center from January 2007 to March 2015.
Results:
Of 55 clinical trials reviewed, 38 required tumor samples for enrolment. Six mandated fresh tumor biopsies, whereas archival samples were permitted for 32 trials. All studies were linked to investigational therapy except one trial of molecular profiling not linked to an investigational treatment. Confirmation of a pre-specified biomarker was required in 23 trials in order to receive investigational treatment. Trial participation was offered to 640 patients at 940 unique study encounters, with some patients enrolling in multiple trials. Of 549 encounters where study treatment was offered, 60% proceeded to receive study treatment. Those considering trials without mandatory tissue requirements were more likely to proceed to study enrolment than those considering trials with these requirements (83% vs. 55%, p<0.0001). Those considering trials permitting use of archival tissue were more likely to begin study treatment than those considering trials mandating fresh research biopsies (59% vs. 38%, p=0.0007). For trials requiring current tumour samples, 127 research biopsies were performed. Participants proceeded to study treatment in 51% of these encounters. Study treatment was not offered for the remaining encounters due to lack of the pre-specified biomarker (28%), insufficient biopsy tissue (6%) or non-biopsy related exclusion criteria (15%). Among all 549 trial encounters, the most common barriers to trial enrollment included lack of the pre-specified biomarker (35%), withdrawal of consent (20%), other study exclusion criteria (16%), insufficient biopsy tissue (10%), deteriorating clinical status (10%) and death (5%). Of 391 encounters for the molecular profiling trial, 72% successfully completed molecular profiling. Twenty-two percent had insufficient tissue for analysis and 3% died prior to completion of molecular profiling.
Conclusion:
With the evolution of personalized medicine, a growing number of NSCLC trials require tumour tissue for treatment eligibility. This has emerged as a significant barrier to clinical trial enrollment. Potential solutions include routine tissue banking at diagnosis, facilitating use of available diagnostic samples (e.g. fine needle aspirates) for trials, development of circulating DNA assays for trials, and more resources for timely tissue acquisition.
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MINI29.13 - Safety and Clinical Implications of Repeat Tumor Biopsy (RTB) in Patients with Advanced Lung Cancer: A Retrospective Institutional Study (ID 3146)
19:40 - 19:45 | Author(s): E.S. Agwa, F. Almeida, A. Haddad, B.R. Bastos, R. Lee, X. Jia, V. Velcheti, P.C. Ma
- Abstract
- Presentation
Background:
Clinical management of lung cancer and personalized cancer therapy have undergone major advances and paradigm shifts in recent years. Repeat tumor biopsy (RTB) at disease progression is not only used for diagnostic confirmation in lung cancer but also has recently been increasingly adopted to profile tumor biomarkers and identify drug resistance mechanisms. However, information on safety and clinical consensus on the use of RTB remain lacking.
Methods:
The aim of this study is to review RTB patterns and safety in advanced lung cancer patients at Cleveland Clinic and its impact on treatment (Rx) decisions. Patients who were diagnosed and underwent RTB for suspected progressive disease between 2007-2013 were included in this retrospective study. Statistical analysis is primarily descriptive.
Results:
The study involved a total of 184 (56% male) patients. Median age at diagnosis was 65Y (21-87). 100 (54%) were treated initially with single modality (Surgery = 41; Chemo = 33; Radiation = 17; targeted therapy = 9) and 83 (45%) with multimodality Rx (2-modality = 57, 3-modality = 26), 1 (1%) unknown. Number of RTB per patient: 1 in 66.3% (n=122), 2 in 20.1% (n=37), 3 in 11.4% (n=21), and 4 in 2.2% (n = 4). The most common procedure employed at 1st RTB was bronchoscopy (44.6%, n = 82), followed by CT-guided biopsy (bx) (20.7 %, n=38), surgery (10.3%, n=19), excision bx (8.2%, n=15), fine needle aspiration of skin & lymph node (LN) (7.6%, n=14), ultrasound guided bx (5.9%, n=11) & others (2.7%, n=5). Lung was the most commonly rebiopsied site (46%) followed by LN (15%). Procedure-related complications were reported in 13 of 181 (7.2%) pts at 1st RTB (data missing in 3 pts), 3 of 61 (4.9%) at 2nd RTB, 1 of 25(4%) at 3rd RTB, and 0 of 4 (0%) at 4th RTB. The 17 (6.2%) complications are shown in the table below. Histologic change was seen in 13 cases, including adeno-to-squamous carcinoma (at erlotinib resistance) and vice-versa, and non-small cell to small cell histology. The T790M-EGFR mutation was noted in 6 cases, the PIK3CA mutation in 1, and a change in ALK translocation status in 3. Medical decision-making was impacted in 16% of cases. Further molecular and genomic analysis of selected cases is in progress.RTB Complications
Complications N=17 (%) Bleeding without hemodynamic compromise 6 (35) Bleeding requiring transfusion 1 (6) Pneumothorax 5 (29) Hemodynamic instability after premedication 1 (6) Cerebral salt wasting 1 (6) Tracheaoesophageal fistula 1 (6) Severe cough 1 (6) Incomplete procedure 1 (6) Deaths 0 (0)
Conclusion:
Our study results show that RTB can be safely performed in lung cancer patients using standard techniques and can impact lung cancer diagnosis and Rx decision-making.
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MINI29.14 - Using a Bayesian Adaptive Phase II Trial Design to Test Multiple Genetic-Marker-Directed Drugs in the National Lung Matrix Trial (ID 1241)
19:45 - 19:50 | Author(s): L.J. Billingham, K. Brock, L.R. Crack, S. Popat, G. Middleton
- Abstract
- Presentation
Background:
The National Lung Matrix Trial is a flagship trial in the United Kingdom being the first to combine the development of a technology platform that screens for multiple genetic aberrations in tumours with testing of multiple novel genetic-marker-directed drugs. The trial is focused on patients with advanced non-small cell lung cancer and currently includes 8 different drugs and 23 different drug-biomarker combinations. The aim of statistical analysis is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation and this paper evaluates the novel statistical design that has been implemented.
Methods:
The primary outcome measure representing signal of activity is best objective response rate (ORR) in most cases and progression-free survival (PFS) in others. Each drug-biomarker combination could be considered as a single arm phase II trial and could have been designed using standard statistical approaches such as Simon’s two stage design. However, a Bayesian adaptive design was chosen because it gives a more realistic approach to decision-making in this complex setting. It has flexibility to make conclusions without fixing the exact sample size which will be important with the uncertainty around the prevalence of each biomarker. The design allows early stopping of recruitment to any drug-biomarker combinations that do not show sufficient promise at an interim analysis to warrant continuation. It also allows, when appropriate, for information about the primary outcome measure to be shared across different biomarker cohorts within any single drug to aid decision-making. Decision-making is based on the posterior probability distribution for the primary outcome measure, given the observed data and any prior knowledge, calculated using bayesian conjugate analysis. For ORR, the critical threshold which defines a signal of activity is 30% for single drugs and 40% for combinations and for PFS the critical threshold is median 3 months. The interim and final sample sizes were selected to ensure the design achieved pre-defined desirable operating characteristics.
Results:
For both ORR and PFS as primary outcomes, sample sizes of 15 and 30 patients per drug-biomarker cohort for interim and final analyses respectively were selected as giving the required operating characteristics. Simulations of trials for single drugs with ORR as the primary outcome showed that this would ensure a high probability (82%) of correctly stopping early when the true ORR was only 10% and a high probability (90%) of correctly recommending further investigation when the true ORR was as high as 40%. Operating characteristics for the combination drug arms were similar. Operating characteristics for trial arms with PFS as the primary outcome are dependent on the recruitment rate and give high probabilities (>95%) of stopping early when the true median PFS is only 1 month and high probabilities (>80%) of recommending further investigation when the true median PFS is as high as 4 months.
Conclusion:
The Bayesian adaptive design with 15 and 30 patients per drug-biomarker cohort for interim and final analyses respectively gives a flexible, efficient design with good operating characteristics to investigate multiple genetic-marker-directed drugs within a single phase II trial.
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MINI29.15 - Discussant for MINI29.11, MINI29.12, MINI29.13, MINI29.14 (ID 3387)
19:50 - 20:00 | Author(s): B.J. Gitlitz
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 30 - New Kinase Targets (ID 157)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K. Park, M. Villalona
- Coordinates: 9/09/2015, 18:30 - 20:00, Four Seasons Ballroom F3+F4
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MINI30.02 - Phase II Study of Defactinib, VS-6063, a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with KRAS Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 2875)
18:35 - 18:40 | Author(s): D. Morgensztern
- Abstract
- Presentation
Background:
KRAS mutations, which occur in approximately 30% of lung adenocarcinoma cases, represent a major unmet clinical need in thoracic oncology. Preclinical studies have demonstrated that KRAS mutant NSCLC cell lines and xenografts with additional alterations in either p53 or INK4a/Arf (CDKN2A) are sensitive to FAK inhibition. Defactinib (VS-6063) is a selective oral inhibitor of FAK. This trial examined the effect of FAK inhibition in patients with KRAS mutant NSCLC and various permutations of p53 and CDKN2A alterations.
Methods:
This multi-center, non-randomized, open-label, multi-cohort trial enrolled patients with advanced KRAS mutant NSCLC who had received at least one prior (platinum-based chemotherapy doublet) line of therapy. The primary endpoint was progression-free survival (PFS) at 12 weeks. Patients were enrolled into one of four cohorts defined by INK4a/Arf and p53 status. In all cohorts, patients received defactinib 400 mg orally BID until disease progression.
Results:
Fifty-three patients with KRAS mutant NSCLC were enrolled across 9 US sites as of the data cut-off date (13-Mar-2015). Forty-seven patients were enrolled to one of the four molecularly defined cohorts. The median age was 62 years (range 33-80); 48% were female. The median number of prior lines of therapy was 3 (range 1-8) 15 (28%) pts met the 12 week PFS endpoint, with one patient achieving a PR. Median PFS was 46 days (range 12-205 days). Eight patients remained on study as of the data cut-off date. Clinical efficacy did not correlate with secondary mutation status across this KRAS mutant population. Adverse events considered at least possibly related to defactinib were experienced by 35 pts (76%). The majority of these were grade 1 or 2. 11 patients (24%) experienced at least possibly related grade 3-5 events, including 2 grade 5 respiratory failure events. Underlying disease was a confounding factor in many pts. The most commonly reported treatment emergent adverse events of any grade were fatigue (24%) and increased bilirubin (24%).
Conclusion:
In pretreated pts with KRAS mutant NSCLC defactinib demonstrates promising clinical activity with disease control rates comparable to other molecularly targeted agents for this pt population. Defactinib was generally well tolerated. Further development is warranted. Clinical trial: NCT01778803.
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MINI 38 - Biology and Prognosis (ID 167)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:R. Tsuchiya, M. Wynes
- Coordinates: 9/09/2015, 18:30 - 20:00, 702+704+706
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MINI38.06 - FP1039/GSK3052230 with Chemotherapy in Patients with Fibroblast Growth Factor (FGF) Pathway Deregulated Squamous NSCLC or MPM (ID 2879)
19:00 - 19:05 | Author(s): D. Morgensztern
- Abstract
- Presentation
Background:
GSK3052230/FP1039 is a soluble fusion protein with the ECD of FGFR1c linked to the hinge and Fc regions of human IgG1 and acts as a ligand trap by sequestering FGFs involved in tumor growth and angiogenesis. In contrast to small molecule FGFR kinase inhibitors, GSK3052230 spares the hormonal FGF ligands, namely FGF19, 21 and 23. GSK3052230 combined with chemotherapy was efficacious in xenograft models of FGFR1-amplified NSCLC and malignant pleural mesothelioma (MPM) with FGF2 mRNA overexpression. A phase I monotherapy study determined 20mg/kg weekly as the maximum feasible dose (MFD) achieving the desired blood concentration, with no maximum tolerated dose (MTD) reached.
Methods:
This study (NCT01868022 funded by GSK) will evaluate the safety and efficacy of GSK3052230 weekly infusion in combination with paclitaxel + carboplatin in previously untreated FGFR1 amplified metastatic sqNSCLC (Arm A), in combination with docetaxel in FGFR1 amplified metastatic sqNSCLC that has progressed after at least 1 line of chemotherapy (Arm B), or in combination with pemetrexed + cisplatin in patients with untreated and unresectable MPM (Arm C). Each arm involves a dose escalation phase utilizing the 3+3 design, followed by an expansion phase up to 30 patients (pts). Key endpoints include the MTD/MFD of GSK3052230 with chemotherapy, safety, response rates and duration.
Results:
Thirty-four pts have been dosed with GSK3052230 at dose levels ranging from 5mg/kg to 20mg/kg in combination with chemotherapy across three Arms, n=15 (A), n=6 (B) and n=13 (C). Baseline characteristics: males/females 29/5; mean age 68.5 years; ECOG PS 0 (n=20), 1 (n=13), 2 (n=1). Most common AEs were: Arm A: asthenia, neutropenia; Arm B: neutropenia, diarrhea, rash; Arm C: decreased appetite, nausea, infusion reaction. Infusion reactions were seen in 8/34 (24%) pts (n=3 Grade (Gr)1, n=3 Gr2, n=2 Gr3). Serious AEs included: Arm A- neutropenia (n=4), fatigue (n=1), asthenia (n=1), fever (n=1), respiratory infection (n=1); Arm B- neutropenia (n=1), abdominal pain (n=1); Arm C-bowel perforation/ischemia (n=1), infusion reaction (n=1), elevated creatinine (n=1). No DLTs have been observed in sqNSCLC pts (Arms A and B). Three DLTs were reported in mesothelioma pts (Arm C 20mg/kg): Gr5 bowel perforation/ischemia, Gr4 elevated creatinine levels and Gr3 infusion reaction. MFD for Arm A is determined at 20mg/kg. Dose escalation is ongoing for Arms B and C. Preliminary PK results revealed no drug-drug interactions. At time of data-cutoff, 10 PR were observed among 23 patients evaluable for efficacy (ORR = 43%) and a clinical benefit rate of 78% with two ongoing subjects on study >300 days. Preliminary efficacy is as follows: Arm A (6 PR, 2 SD, 1 PD, 6= not-yet-evaluable (NE)), Arm B (4 SD, 1 PD, 1 NE), and Arm C (3 PR, 3 SD, 3 PD, 4 NE).
Conclusion:
GSK3052230 is in general well tolerated in combination with chemotherapy. The MFD for GSK3052230 is 20mg/kg in combination with paclitaxel + carboplatin in first line sqNSCLC patients. Toxicities typically associated with small-molecule FGFR inhibitors, namely hyperphosphatemia and retinal, nail, and skin changes, were not observed. The initial activity and safety profile of GSK3052230 warrant further study.
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ORAL 10 - SCLC (ID 98)
- Event: WCLC 2015
- Type: Oral Session
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:C. Faivre-Finn, P. Lara Jr.
- Coordinates: 9/07/2015, 10:45 - 12:15, 605+607
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ORAL10.01 - A DLL3-Targeted ADC, Rovalpituzumab Tesirine, Demonstrates Substantial Activity in a Phase I Study in Relapsed and Refractory SCLC (ID 1598)
11:05 - 11:16 | Author(s): D. Morgensztern
- Abstract
Background:
Rovalpituzumab tesirine (i.e. SC16LD6.5) is a Delta-like protein 3 (DLL3) targeted antibody-drug conjugate (ADC) comprised of a humanized monoclonal antibody, dipeptide linker, and pyrrolobenzodiazepine (PBD) dimer toxin with a drug-to-antibody ratio of 2. DLL3 is highly expressed in human neuroendocrine tumors and their tumor-initiating cells, including approximately two-thirds of small cell lung cancer (SCLC). DLL3 is not expressed at detectable levels in normal tissues. Rovalpituzumab tesirine induced tumor regression and prolonged time to progression significantly outperforming cisplatin/etoposide in DLL3-expressing SCLC patient-derived xenograft tumor models. Based on this promising activity, a first-in-human phase I trial in patients (pts) with recurrent SCLC was initiated and preliminary results are reported below.
Methods:
SCLC pts with progressive disease after 1 or 2 previous lines of therapy received escalating doses of rovalpituzumab tesirine as a single agent once every 3 weeks (Q3W) in 1-3 pt cohorts until dose limiting toxicities (DLTs) were observed. The doses were 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg Q3W. Midway through accrual, pharmacokinetic data revealed a longer than expected ADC half-life of ~11 days, prompting evaluation of a Q6W schedule. A DLL3 antibody was developed and utilized to assess antigen expression in archived tumor specimens. Biomarker positive (BM+) tumors were defined by IHC membrane-associated H-Scores ≥ 120.
Results:
52 pts were treated: 34 Q3W and 18 Q6W; 24F/28M; median age, 61 years (44-82). Acute and chronic DLTs of thrombocytopenia and capillary leak syndrome (CLS) were observed at 0.8 and 0.4 mg/kg Q3W, respectively. Maximum tolerated doses (MTD) of 0.2 mg/kg Q3Wx3 cycles and 0.3 mg/kg Q6Wx2 cycles were further evaluated in expansion cohorts. The most common treatment emergent adverse events of any grade among all pts were fatigue (40%), rash (39%), nausea (29%), dyspnea (23%), decreased appetite (21%) and vomiting (21%). Grade 3+ CLS and thrombocytopenia were seen in 7 (14%) and 3 (6%) pts, respectively, with no reported Grade 5 toxicity. Of 38 archived tumor specimens received from enrolled pts, 23 (61%) were DLL3 BM+. Among the 16 confirmed DLL3 BM+ pts treated at the MTDs, 7 pts (44%) had partial response (PR) and 8 pts (50%) achieved stable disease (SD) for a combined clinical benefit rate (CBR) of 94%. In all evaluable pts treated at the MTD without regard for DLL3 biomarker status (n=32), the ORR was 22% (n=7 PR) and SD 53% (n=17), for a CBR of 75%. Notably, all pts with PRs that were treated at the MTD, and those having the most durable clinical benefit (up to 569 days OS), were BM+. Similar response rates were observed among pts sensitive and refractory to first-line therapy, and in the third-line setting where no standard-of-care currently exists.
Conclusion:
Rovalpituzumab tesirine, a first-in-class DLL3-targeted ADC, has manageable toxicity and demonstrated significant anti-tumor activity (44% ORR and 95% CBR) as a single agent in second- and third-line pts with recurrent DLL3 BM+ SCLC. A pivotal study is being planned.
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ORAL 21 - Biology - Moving Beyond the Oncogene to Oncogene-Modifying Genes (ID 118)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:A. Katz, M.S. Tsao
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 4a-4f
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ORAL21.04 - Discussant for ORAL21.01, ORAL21.02, ORAL21.03 (ID 3354)
11:18 - 11:28 | Author(s): D. Morgensztern
- Abstract
- Presentation
Abstract not provided
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-004 - Oncologists' Comprehension and Beliefs Surrounding Cancer Immunotherapy in Advanced NSCLC (ID 1267)
09:30 - 09:30 | Author(s): D. Morgensztern
- Abstract
Background:
Advanced NSCLC is now recognized as an immune-modifiable disease, and with the approval of the first PD-1 inhibitor, immune checkpoint inhibitors represent a new standard of care for patients with previously treated squamous cell lung cancer. The objective of this study was to evaluate oncologists’ familiarity with cancer immunotherapy in the context of advanced NSCLC and the impact of an educational curriculum on narrowing gaps in clinical practices.
Methods:
An expert panel of oncologists identified educational gaps in the area of cancer immunotherapy. A series of 9 CME online activities were developed, 2 of which centered on advanced NSCLC and are the focus of this study. Interactivity questions allowed learners to self-report their familiarity with immunotherapy concepts in the management of advanced NSCLC, while case vignette and knowledge-based questions were constructed around evidence-based medicine. Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to all analyses.
Results:
1368 oncologists participated in the 2 activities on advanced NSCLC. As seen in the table below participation in the education activities resulted in numerous improvements in knowledge and competence as seen in the table below. Despite improvements, several important gaps remained. Only70% of oncologists comprehend that a tumor may increase in size or new lesions appear during initial therapy with an immune checkpoint inhibitor. In addition, about half of oncologists still had difficulty grasping how immune checkpoints downregulate T cell responses. Finally, oncologists still had difficulty identifying the unique side effect profile associated with immune checkpoint inhibitors. In addition, 55% of oncologists reported they were not comfortable with managing side effects associated with these agents.Table
% answered correctly % answered correctly Pre-Activity Post-Activity Comprehension of Basic Immunology Interaction of TCR with MHC-peptide complex and co-stimulatory receptors CD28/CD80 and CD86 52% 69% Which does not represent a role of an immune checkpoint in the adaptive immune response: CTLA-4 binds to CD28, augmenting T-cell activation 50% 57% Knowledge of Immune System’s Role in Response to Cancer T cell infiltration and decreased risk of recurrence 69% 76% Disease progression on an immune checkpoint inhibitor 65% 71% Efficacy, Safety, Limitations of Immune Checkpoint Inhibitors Limitations PD-L1 as a biomarker 26% 70% Durability of response 5% 30% Unique side effect profile 41% 59%
Conclusion:
The study evaluated oncologists’ familiarity with cancer immunotherapy in advanced NSCLC and demonstrated the necessity of developing targeted educational interventions for improving the knowledge and practice patterns of oncologists. Additional education is needed to continue to improve clinicians’ competence in the use of cancer immunotherapies in the management of NSCLC.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-089 - Nab-Paclitaxel with or without CC-486 as Second-Line Therapy for NSCLC (ABOUND.2L) (ID 719)
09:30 - 09:30 | Author(s): D. Morgensztern
- Abstract
Background:
Many patients with advanced non-small cell lung cancer (NSCLC) will experience disease progression during first-line chemotherapy. Effective and well-tolerated second-line treatment options for this patient population are limited. In a multicenter phase III trial, first-line treatment with nab-paclitaxel plus carboplatin (nab-P/C) significantly improved the primary endpoint of overall response rate (ORR) compared with solvent-based paclitaxel plus C in patients with advanced NSCLC (33% vs 25%; P = 0.005; Socinski et al. J Clin Oncol. 2012;30:2055-2062). nab-P combined with CC-486, an oral formulation of azacitidine, resulted in promising outcomes in a phase I trial of patients with relapsed/refractory solid tumors (LoRusso et al. Mol Cancer Ther. 2013;12(11 Suppl):Abstract A120). In the open-label, multicenter phase II ABOUND.2L trial, the safety and efficacy of nab-P with or without CC-486 will be evaluated in the second-line treatment of patients with advanced nonsquamous NSCLC.
Methods:
Approximately 160 patients who have received 1 platinum-containing chemotherapy regimen for treatment of advanced disease will be randomized 1:1 to CC-486 200 mg/day on days 1 to 14 every 21 days plus nab-P 100 mg/m[2] intravenously (IV; 30-minute infusion) on days 8 and 15 every 21 days or nab-P 100 mg/m[2] IV (30-minute infusion) on days 1 and 8 every 21 days. Key eligibility criteria include histologically or cytologically confirmed advanced nonsquamous NSCLC, ECOG performance status ≤ 1, adequate organ function, no active brain metastases, no prior taxane therapy, no known EGFR mutation or EML4-ALK translocation, and peripheral neuropathy grade < 2. Randomization will be stratified by ECOG performance status (0 vs 1), sex, and smoking status (yes vs no). ClinicalTrials.gov identifier NCT02250326.Key Endpoints
Primary -Progression-free Survival Secondary -Disease control rate -Overall Survival -ORR -Safety Exploratory -Changes in quality of life -Healthcare resource utilization throughout the study -Correlation between pretreatment tumor characteristics and response to treatment
Results:
Not applicable
Conclusion:
Not applicable
