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T.K. Owonikoko
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.14 - Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH): Descriptive Analysis and Overall Survival (ID 3153)
18:00 - 18:05 | Author(s): T.K. Owonikoko
- Abstract
- Presentation
Background:
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by proliferation of neuroendocrine cells in the bronchial wall and considered to be pre-invasive lesion for lung carcinoid tumors [1]. There is increasing rate of diagnosis of this condition due to widespread availability and use of cross sectional imaging. DIPNECH is reported as an incidental finding in approximately 5.4% of patients undergoing resection for lung neoplasms [2]. The optimal management of this condition is currently not well-established. The limited data regarding the clinicopathologic characteristics and long term outcome for patients with DIPNECH provided a strong rationale for this study.
Methods:
We employed medical records to obtain demographic, clinical characteristics and survival for patients diagnosed with DIPNECH at our institution between January 1990 to December 2014. A review of archival diagnostic material was conducted by expert pulmonary pathologists to confirm the original diagnosis. Differences in clinical characteristics and survival was assessed between patient groups defined by race, gender, age, smoking status, body habitus and treatment received. Survival was computed using the Kaplan–Meier method while univariate and multivariate models were employed to assess for significant association between patient survival and variables of interest.
Results:
A total of 27 patients were included in this analysis. The majority of patients were females (89%) and predominantly of Caucasian (66.7%) or Black (14.8%) race. The median age at diagnoses was 63 years (range: 20-77) and 61.5% of patients were non-smoker. Approximately 52% underwent surgical resection. The median overall survival (OS) was 151 months (95%CI: 39-165) while 1-year and 5-year survival rates were 95.2% and 73.2% respectively. Nineteen patients (71%) remain alive at the time of this analysis. Male patients (HR: 4.58, 95%CI: 0.76-27.67, p=0.098) and smokers (HR: 23.79; 95%CI: 0.98-579.54; p<0.052) appeared to have an inferior survival. No statistically significant difference in survival was recorded in patient subgroups defined by age, race, surgical intervention or body weight.
Conclusion:
DIPNECH is a rare condition with increasing rate of diagnosis. The overall prognosis is good in comparison to other lung neoplasms but up to a quarter of the patients do not survive beyond five years post diagnosis. Male gender and associated use of tobacco products may be associated with poor outcome. References: 1. Chassagnon, G., et al., DIPNECH: when to suggest this diagnosis on CT. Clin Radiol, 2015. 70(3): p. 317-25. 2. Ruffini, E., et al., The significance of associated pre-invasive lesions in patients resected for primary lung neoplasms. Eur J Cardiothorac Surg, 2004. 26(1): p. 165-72.
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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: 1
- 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): T.K. Owonikoko
- 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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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.09 - Discussant for MINI37.05, MINI37.06, MINI37.07, MINI37.08 (ID 3445)
19:15 - 19:25 | Author(s): T.K. Owonikoko
- Abstract
- Presentation
Abstract not provided
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MTE 09 - Treatment of Advanced SCLC Including Second Line (Ticketed Session) (ID 61)
- Event: WCLC 2015
- Type: Meet the Expert (Ticketed Session)
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 07:00 - 08:00, 708+710+712
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MTE09.01 - Treatment of Advanced SCLC Including Second Line (ID 1990)
07:00 - 07:30 | Author(s): T.K. Owonikoko
- Abstract
- Presentation
Abstract:
Chemotherapy is the bedrock of advanced SCLC management. Platinum-based chemotherapy is the most widely employed regimen in the frontline setting.[1] Systemic therapy is administered for SCLC in different settings including frontline, maintenance and salvage settings. Frontline Therapy: The clinical efficacy of frontline chemotherapy does not significantly differ based on the choice of partner chemotherapy employed along with platinum particularly in non-Japanese patients. The limited impact of the established frontline chemotherapy regimen is highlighted by the fact that lass than 25% of patients with extensive stage SCLC survive past 2 years. Nonetheless, population-based analysis of real-world patient outcome showed survival benefit of chemotherapy whereas the outcome for untreated patients has not improved in the last 20 years.[2] Attempts to improve on treatment efficacy through intensification of chemotherapy regimens have met with uniform failure with heightened toxicity and no significant survival benefit. Incorporation of targeted biologic agents showed some promise in the preclinical and clinical settings. The addition of antiangiogenic agent to standard platinum-based doublet showed a non significant but positive trend towards improved survival. The SALUTE trial enrolled and randomly assigned 52 patients to receive standard platinum-doublet along with bevacizumab or placebo.[3] The median PFS and RR were higher in the bevacizumab group (5.5 vs. 4.4 months; hazard ratio [HR], 0.53; 95% CI, 0.32 to 0.86) and 58% (95% CI, 43% to 71%) vs. 48% (95% CI, 34% to 62%). The median overall survival (OS) was no different (HR of 1.16; 95% CI, 0.66 to 2.04).[3] E3501 study also evaluated the benefit of antiangiogenic therapy in a 63-patient single arm study treated with cisplatin, etoposide and bevacizumab.[4] The response rate was 63.5%, median PFS of 4.7 months and OS was 10.9 months. Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels. Using a different partner chemotherapy of carboplatin, irinotecan and bevacizumab, Spigel et al. reported an ORR of 84% (95% CI 71-93%), median TTP of 9.13 months (95% CI 7.36-9.46 months) and median OS of 12.1 months.[5] Identification of a reliable predictive biomarker would be critical for this management strategy to proceed beyond the completed phase II trials. Similarly, the E1508 study combined inhibitors of the hedgehog developmental pathway (vismodegib; GDC0049) and insulin-like growth factor receptor (cixutumumab; IMCA12) with platinum-doublet chemotherapy and compared the clinical outcome to platinum-doublet only. There was no improvement in median PFS (4.7, 4.4, 4.6 months) or OS (9.4, 9.8, 10.1 months).[6] The combination of ipilimumab, an immune checkpoint inhibitor targeting CTLA4, with platinum doublet chemotherapy was very promising as a frontline regimen in SCLC especially when administered in a phased schedule.[7] The study randomized 130 patients with chemotherapy-naïve SCLC-ED in a 1: 1: 1 ratio to receive paclitaxel/carboplatin with placebo (control), ipilimumab concurrent with paclitaxel/carboplatin or phased ipilimumab following induction paclitaxel/carboplatin. Phased ipilimumab improved irPFS versus control [HR =0.64; P=0.03] with median irPFS of 6.4 vs. 5.3 months and median OS of 12.9, vs. 9.9 months. This promising result provided the rationale for a phase III study of this regimen in newly diagnosed SCLC-ED. Maintenance or Consolidation Therapy: The strategy of maintenance or consolidation therapy has been systematically evaluated in SCLC-ED following completion of frontline doublet chemotherapy. Topotecan was investigated as a maintenance therapy in E7593 study, a phase III trial that randomized patients with stable or responding disease following induction doublet chemotherapy to observation or four cycles of topotecan. A total of 223 were randomized to observation (n-111) or topotecan (n = 112). The PFS associated with consolidation topotecan was 3.6 months v 2.3 months (P <.001) for observation but without any significant difference in OS between the observation and topotecan arms (8.9 months v 9.3 months; P =.43).[8] Similarly, E1500 evaluated temsirolimus as maintenance therapy following frontline therapy of SCLC-ED. The study enrolled 87 patients with either stable or responding disease following induction platinum-doublet to receive temsirolimus (25mg or 250mg) every week until disease progression. The median and 1-year PFS were 2.2 months (95% CI: 1.8, 2.9) and 4.7% (95% CI: 0.2%, 9.2%), respectively. The median OS was 8 months (95% CI: 6.5, 9.5). Both topotecan and temsirolimus failed to show clinical benefit as consolidation or maintenance therapy following frontline doublet chemotherapy.[9] However, sunitinib as a maintenance therapy was associated with improved PFS in SCLC-ED. The CALGB 30504 trial was a randomized phase II study that enrolled patients without progression to placebo or sunitinib. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). The median PFS was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; P = 0.16). A phase III study to confirm this positive finding is currently in planning.[10] Salvage Therapy: The poor outcome associated with SCLC is due primarily to the refractoriness of relapsed disease to salvage therapy.[11] Although a number of agents have shown activity in relapsed SCLC including irinotecan, paclitaxel, bendamustine, etoposide and gemcitabine, topotecan remains the only approved agent for the treatment of relapsed SCLC in Western countries. Amrubicin showed positive efficacy and is an approved agent in Japan for relapsed SCLC. However, it failed to demonstrate superior efficacy over topotecan in a randomized phase III study conducted in the West. A total of 637 patients were randomized to amrubicin or topotecan. The median PFS was 4.1 vs. 3.5 months (HR, 0.802; P = .018); median OS was 7.5 months vs. 7.8 months (HR: 0.880; P = .170); with amrubicin and topotecan respectively.[12] Immune checkpoint inhibitors targeting PD-1 signaling (nivolumab; pembrolizumab) and CTLA4 pathways (ipilimumab) are currently being evaluated in relapsed SCLC. Initial reports showed encouraging activity of this class of therapeutic agents with superior efficacy noted with combination therapy over single agent and potential enrichment for patients likely to benefit with the use of PD-L1 expression as a predictive biomarker.[13][, ][14] Perspectives on the future: E2511 is an ongoing phase II study exploring whether the addition of a PARP inhibitor to platinum doublet will result in improved clinical outcome. There is preclinical support and biological rationale to expect that PARP inhibitor therapy will enhance the efficacy of DNA-damage inducing chemotherapy regimen. The study completed accrual in the 2[nd] quarter of 2015 and results are awaited. The genomics of SCLC is significantly understudied in comparison to the non-small cell lung cancer and other cancer types. Recent works using state of the art genomic assays confirmed previously known frequent alterations in RB, TP53 and Myc family genes.[15][, ][16] These works also identified hitherto unknown driver alterations in other genes such as the SOX family of genes. Advancement in the management of SCLC in the coming years is most likely to emanate from the integration of immunecheckpoint blockade into standard treatment paradigm for SCLC as well as through successful exploitation of the frequent genetic and epigenetic alterations that characterize this disease for targeted therapeutics. References: 1. Pillai RN, Owonikoko TK. Small cell lung cancer: therapies and targets. Seminars in oncology 2014;41:133-142. 2. Behera M, Ragin C, Kim S, et al. Trends in small cell lung cancer (SCLC) survival: Predictors and impact of systemic therapy. J Clin Oncol 2014;32:abstr 7599. 3. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol 2011;29:2215-2222. 4. Horn L, Dahlberg SE, Sandler AB, et al. Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. J Clin Oncol 2009;27:6006-6011. 5. Spigel DR, Greco FA, Zubkus JD, et al. Phase II trial of irinotecan, carboplatin, and bevacizumab in the treatment of patients with extensive-stage small-cell lung cancer. J Thorac Oncol 2009;4:1555-1560. 6. Belani CP, Dahlberg SE, Rudin CM, et al. Three-arm randomized phase II study of cisplatin and etoposide (CE) versus CE with either vismodegib (V) or cixutumumab (Cx) for patients with extensive stage-small cell lung cancer (ES-SCLC) (ECOG 1508). J Clin Oncol 2013;31:abstr 7508). 7. Reck M, Bondarenko I, Luft A, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 2013;24:75-83. 8. Schiller JH, Adak S, Cella D, et al. Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2001;19:2114-2122. 9. Pandya KJ, Dahlberg S, Hidalgo M, et al. A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). J Thorac Oncol 2007;2:1036-1041. 10. Ready NE, Pang HH, Gu L, et al. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol 2015;33:1660-1665. 11. Owonikoko TK, Behera M, Chen Z, et al. A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol 2012;7:866-872. 12. von Pawel J, Jotte R, Spigel DR, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 2014;32:4012-4019. 13. Antonia SJ, Bendell JC, Taylor MH, et al. Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. J Clin Oncol 2015;33:suppl; abstr 7503. 14. Ott PA, Fernandez MEE, Hiret S, et al. Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028. J Clin Oncol 2015;33. 15. Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nature genetics 2012;44:1111-1116. 16. Peifer M, Fernandez-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nature genetics 2012;44:1104-1110.
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ORAL 05 - Surgery (ID 97)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:P. Van Schil, F.(. Kong
- Coordinates: 9/07/2015, 10:45 - 12:15, 201+203
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ORAL05.05 - Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis (ID 2962)
11:48 - 11:59 | Author(s): T.K. Owonikoko
- Abstract
Background:
Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the optimal approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society.
Methods:
The NCDB was queried from 2003-2011 for NSCLC pts diagnosed with stage IIIA-N2 disease and treated with chemotherapy and radiation (CRT). Data was extracted on patient demographics, tumor pathology, treatments and outcomes. Three cohorts of pts were studied - CRT only/no surgery (NS), CRT + lobectomy (L) and CRT + pneumonectomy(P). The univariate and multivariable analyses (MV) were conducted using Cox proportional hazards model and log rank tests. All analyses were performed using SAS Version 9.3.
Results:
A total of 29,584 pts were included in this analysis: NS-91.7%, L-7%, and P-1.5%. Pt characteristics: median age 66 years (yrs); males 56%; whites 86%; academic centers 27%; metro locations 78%; government insured 63%; Charlson/Deyo comorbidity score 0 in 66%. Pts < 60 yrs were more likely to receive TT- L (47%), P (60%) vs. NS (29%); p<0.001. Pts in academic centers were more likely to get TT than NS (42% vs. 25%). On MV analysis, L and P had significantly better survival vs. NS: HR 0.43 (0.38-0.48) and HR 0.57 (0.46-0.71) respectively; p <0.001. The median survival of L, P and NS were 44.5 m vs. 25.6 m vs. 15.7 m (p<0.001) and 5- year survival rates (SR) were 44% vs. 33% vs. 14% respectively. 30-day mortality was higher in P vs. L [7% vs. 2.6%; OR 0.26(0.16-0.45); p<0.001]. Pts with <2 lymph nodes (LN) had better survival than pts with >2 LNs in L (50% vs. 37%; 60m vs. 38.8m) but worse in NS (13.8% vs.16.4%; 15.3m vs.18.5m). On MV analysis of LNs, L had better survival than NS: HR 0.4 (0.35-0.46) in <2 LN pts and HR 0.56 (0.46-0.69) in ≥2 LN pts; p<0.001. In pts with <2 LN, L had better survival than P (60m vs. 25.5m; p<0.0001). L and P had better SR than NS in all ages: 48% vs.37% vs. 19% in ≤60 yrs; 42% vs. 30% vs.14% in 61-70 yrs, 36% vs.19% vs. 10% in >70 yrs.
Conclusion:
TT was utilized in less than 10% of pts with stage IIIA-N2 disease, suggesting high degree of pt selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.01 - A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin-Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients (ID 600)
10:45 - 10:56 | Author(s): T.K. Owonikoko
- Abstract
- Presentation
Background:
The two most commonly used chemotherapy regimens deployed concurrently with thoracic radiation (RT) for patients with unresectable IIIA and IIIB non-small cell lung cancer (NSCLC) are carboplatin/paclitaxel (CP) and cisplatin/etoposide (CE). Because there are no prospective comparisons of these two regimens in this setting, we conducted a systematic review of published trials to compare outcomes and toxicities between CE and CP.
Methods:
Studies which enrolled stage III patients receiving RT with CP or CE were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase I, enrolled less than 10 pts, or included surgical resection. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2) software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), response rate (RR) and toxicities. Two-tailed T-test with a significance level of 0.05 was used for all comparisons.
Results:
3194 patients were included from 32 studies in the CE arm, and 3789 patients from 51 studies in CP. Baseline characteristics of patients on the CE arm versus CP arm were: median age 61 vs. 63 years, male 67.6% vs. 78%, squamous histology 39% vs. 40%, and median radiation dose 62 Gy vs. 63 Gy. There was no significant difference in response rates between CE and CP (65% vs. 56%, p =0.6), respectively. There was no significant difference in median progression free survival (11.5m vs. 9.3m p =0.2), overall survival (19.8m vs. 18.4m, p=0.48), 1-year survival rate (66% vs. 65%, p=0.8), or 3-year survival rate (31% vs. 25%, p=0.4) for CE vs. CP. CE was associated with higher grade 3/4 hematological toxicities than CP, such as neutropenia (53% vs. 23% p<0.0001), thrombocytopenia (14% vs. 6% p=0.001), anemia (16% vs. 8% p=0.06), as well as grade 3/4 nausea/vomiting (20% vs. 9% p=0.018), while rates of grade 3/4 pneumonitis and esophagitis were similar.
Conclusion:
CE and CP regimens were associated with comparable efficacy when used with concurrent radiotherapy for stage III unresectable NSCLC pts. The toxicity profile favored the CP regimen.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-020 - Survival Impact of Adjuvant Radiation and Chemotherapy in Patients with Typical and Atypical Pulmonary Carcinoids (ID 3054)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
Adjuvant chemotherapy or radiation is commonly employed after resection of primary pulmonary carcinoid especially for patients with advanced stage disease with expectation of survival benefit. The indication for adjuvant therapy is poorly defined and there are limited data in support of this clinical practice. We therefore evaluated predictors and potential benefit of adjuvant chemotherapy and radiation using the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society
Methods:
The NCDB was queried for patients who had undergone surgical resection of pulmonary carcinoid tumors between 2003 and 2006. Patients younger than 18 years and those with incomplete survival data were excluded from this analysis. Overall survival was defined as time from date of definitive surgery to date of death or last follow-up. Univariate and multivariable models were employed to assess for association between patient survival and variables of interest. Gender, age, and race were fit in a multivariable Cox model with treatment, and backward selection criteria (alpha = 0.1) were used to determine whether education, urban/rural, tumor size, income, laterality, insurance, or comorbidity score were included in the model. The proportional hazards assumption was checked for all models.
Results:
We included 4984 eligible patients diagnosed between 2003 and 2006 in the analysis. Post resection adjuvant radiation was administered to 4.2% of the patients; 1.9% received chemotherapy while the remaining patients did not receive any adjuvant therapy. Patients treated with adjuvant chemotherapy or radiation had worse survival at 2 years post surgery (75.7% and 70.8%% respectively) in comparison to patients managed with surgical resection only (94.2%). This survival difference was still significant in multivariable Cox models after adjusting for relevant patient and prognostic factors including gender, age, race, stage, lymph node involvement, tumor size, education level and co-morbidity score (HR: 2.35, 95% CI: 1.43 - 3.85, p<0.001 and HR: 1.97, 95% CI:1.48 - 2.61, p<0.001 for adjuvant chemotherapy and radiation, respectively). Decreased survival persisted in analyses restricted to patients with lymph node involvement (HR 1.58, p 0.084 and 3.21, p<0.001 for chemotherapy and radiation, respectively), and with advanced stage cancer (HR 4.10, p <0.001 and 2.04, p=0.036 and for radiation and chemotherapy, respectively) . Results did not differ by histology
Conclusion:
We observed worse outcomes in patients with typical and atypical carcinoid treated with adjuvant chemotherapy and radiation post surgery. The poor outcome associated with adjuvant therapy may be explained in part by the fact that patients considered for adjuvant therapy are more likely to have advanced stage disease and adverse tumor characteristics. However, contribution from potential toxicities of chemotherapy and radiation cannot be entirely excluded pending additional analysis in propensity-matched cohorts of patients.
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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: 3
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-011 - Relationship between EGFR Mutation Status and Response to Specific Chemotherapeutic Agents in Patients with Stage IV Non-Small Cell Lung Cancer (ID 2491)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
The purpose of this study was to investigate whether outcomes with various chemotherapy regimens were affected by the specific epidermal growth factor receptor (EGFR) mutations in patients with stage IV non-small cell lung cancer (NSCLC).
Methods:
We retrospectively analyzed the association between the different EGFR mutations (exon 19 deletion, exon 21, and 18 mutations) and their response to chemotherapy. A total of 17 patients with stage IV NSCLC treated at Winship Cancer Institute of Emory University between January 2007 and February 2015 who received chemotherapy were investigated retrospectively, and their clinical date were assessed according to EFGR mutation.
Results:
14 (82.4%) females and 3 (17.6%) males were identified harboring EGFR mutations. Median age at the time of diagnosis was 66 years (SD 14.08). 12 patients (70.6%) were never smokers, and 5 (29.4%) were former or current smokers. EGFR exon 19 deletion was present in 7 patients (41.2%), exon 21 mutation in 8 (47.1%), and exon 18 in 2 (11.8%). 15 (88.2%) received chemotherapy, and 11 (64.7%) received pemetrexed-based treatment. Four patients had partial response (PR) as the best response to pemetrexed-based chemotherapy, and all of them harbored exon 21 mutation. Among patients that received other types of chemotherapies (paclitaxel, gemcitabine, navelbine and platinum), 6 with exon 21 mutation, and 2 with exon 19 deletion experienced PR. Progression-free survival (PFS) was not significantly different among the groups of mutation (p=0.3645) that received paclitaxel, gemcitabine, navelbine and platinum as chemotherapies, and PFS was also not different for pemetrexed-based regimen (p=0.4569).
Conclusion:
We did not find differential sensitivity to various chemotherapy agents based on mutation type in advanced NSCLC patients harboring an EGFR mutation.
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P2.01-068 - Androgen Deprivation Therapy for Prostate Cancer Associated with Improved Survival in Non Small Cell Lung Cancer: A SEER-MEDICARE Analysis (ID 2743)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
Cancer of the prostate and lung are most commonly diagnosed in the elderly. Aberrant female sex hormone signaling has been well-described in NSCLC. The impact of androgen deprivation therapy (ADT) on non-small cell lung cancer (NSCLC) outcome has, however, not been well studied.
Methods:
We employed the linked SEER-MEDICARE database to assess the potential impact of ADT on NSCLC. We analyzed data from patients diagnosed with NSCLC between 1985 and 2005 and registered in the SEER-MEDICARE database. Patients were categorized into three groups: prostate cancer diagnosis followed by NSCLC (PL), NSCLC followed by prostate cancer (LP) and NSCLC only (L). Demographic and survival outcomes were compared between these groups. The impact of sequence of cancer diagnosis and ADT on survival post NSCLC diagnosis was assessed within the PL group using logistic regression model. Cox proportional hazards models were employed to estimate the effect of ADT and stage of prostate cancer on survival with adjustment for significant prognostic factors.
Results:
A total of 417630 patients were included in this analysis; male/female (56.4%/43.6%); Race: White (84.0%), Black (9.0%), Asian (2.1%), Hispanic (1.0%), others (3.0%); Stage: I (17.4%), II (2.9%), III (33.6%) and IV (46.1%). The majority of the patients were in the L group (96.3%), followed by PL (2.9%) and LP (0.8%). Patients in the LP group had the best 12-month survival rates (84.5%), followed by L (44.4%) and PL (40.1%). Analysis within the PL group showed an inverse correlation between stage of prostate cancer diagnosis and interval of time to NSCLC diagnosis: 54.8, 54.1, 62.1 and 59.3 months for stage I, II, III and IV prostate cancer, respectively. Prostate cancer patients exposed to ADT had a shorter interval to lung cancer diagnosis (48.3 vs. 52.7 months; p < 0.001). On multivariate analysis, patients exposed to ADT had a higher median survival (10 months vs. 9 months; p < 0.001) and reduced risk of death (HR:1.11; 95%CI:1.05-1.18), p <0.001).
Conclusion:
ADT therapy for prostate cancer was associated with improved survival for subsequent NSCLC diagnosis. Our result supports systematic exploration of ADT as a treatment strategy for NSCLC.
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P2.01-090 - A Phase 2, Single Arm Study of Lucitanib in Patients with Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF-Related Genetic Changes (ID 2878)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors A/B (PDGFRA/B). Clinical activity was observed in a phase 1/2 study of lucitanib monotherapy in cancer patients with tumor amplification of FGF-related genes or in tumors with predicted sensitivity to VEGF inhibitors. Genomic evidence of FGF, VEGF or PDGF axis aberrancy is seen in up to 15% of patients with lung cancer, which provides a strong rationale to assess lucitanib in this setting.
Methods:
The current study evaluates daily oral lucitanib monotherapy in 40 patients with amplification or activating mutations in FGF, VEGF or PDGF-related genes. This is an international, multicenter, open-label, single-arm study. The primary endpoint is objective response rate (ORR; RECIST 1.1) with secondary endpoints of response duration, clinical benefit rate, progression-free survival, and safety. Exploratory objectives include volumetric assessment of tumor growth kinetics, serial circulating tumor DNA measurement, and identification of additional biomarkers of lucitanib activity. Key inclusion criteria include: patients with advanced/metastatic non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) or large cell lung cancer and tumor tissue evidence of relevant genomic aberrancies. Patients must have measurable disease and at least one previous treatment for advanced disease. Key exclusion criteria include: carcinoid histology, symptomatic CNS metastases, anti-cancer treatment for lung cancer within 28 days or 5 half-lives before first dose of lucitanib. This study is enrolling patients in the United States and Europe at centers skilled in the identification of patients with relatively uncommon genetic tumor alterations.
Results:
not applicable
Conclusion:
not applicable
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-010 - Alisertib (MLN8237)+Paclitaxel versus Placebo+Paclitaxel for Relapsed SCLC (ID 1158)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
Small cell lung cancer (SCLC) is an aggressive malignant disease comprising approximately 14% of all lung cancers, with approximately 31,000 new diagnoses each year in the USA. SCLC has a very poor prognosis, particularly in patients presenting with extensive stage disease. Platinum-based combinations are standard first-line therapy for SCLC; however, relapse is almost universal (≥85%) and patients require further treatment in subsequent lines. Effective new targeted therapies are needed to improve the poor outcomes observed in SCLC. Alisertib is an investigational, orally available, selective inhibitor of Aurora A kinase. Alisertib has shown single-agent antitumor activity in preclinical in vivo models of SCLC and has demonstrated synergism with paclitaxel in this setting. Single-agent alisertib has demonstrated promising efficacy in patients with relapsed/refractory SCLC (Melichar B, et al. Lancet Oncol 2015;16[4]:395–405). Further, phase 1 and 2 evaluation of alisertib+paclitaxel in patients with relapsed ovarian cancer and breast cancer has suggested the antitumor activity of this combination (Falchook G, et al. Int J Gynecol Cancer 2013;23[8] Suppl_1:abstract; Coleman R, et al. Ann Oncol 2014;25[Suppl_4]:abstract 876O). Here we describe the design and objectives of an ongoing phase 2, randomized, double-blind, placebo-controlled study of alisertib+paclitaxel versus placebo+paclitaxel in patients with relapsed SCLC and previously treated with only one line of platinum-based therapy (NCT02038647).
Methods:
Approximately 166 adult patients with relapsed SCLC after standard first-line platinum-based therapy, measurable disease by RECIST v1.1, and Eastern Cooperative Oncology Group performance status 0 or 1 will be enrolled at approximately 80 sites in the USA and Europe. Patients will be randomized 1:1 (stratified by type of relapse [sensitive vs resistant/refractory] and presence of brain metastases) to receive 28-day cycles of either alisertib 40 mg or matched placebo PO twice daily on days 1−3, 8−10, and 15−17, plus paclitaxel 60 or 80 mg/m[2 ]IV, respectively, on days 1, 8, and 15, until disease progression or unacceptable toxicity. The primary endpoint of the trial is progression-free survival (PFS). Assuming a hazard ratio of 0.6 for PFS, a total of 138 progression/death events will be required to provide 85% power (two-sided alpha=0.05). Secondary endpoints include: overall and complete response rates; disease control rate; duration of response; overall survival; safety (NCI-CTCAE v4.03); alisertib pharmacokinetics; and symptom-related endpoints (symptom score, time to symptom relief, time to symptom progression). Evaluation of candidate biomarkers in tumor tissue specimens and in circulating tumor cells (CTC)/circulating tumor DNA, change from baseline in CTC numbers, and health-related quality of life (EORTC QLQ-C30/QLQ-LC13 instruments) are exploratory endpoints. As of 10 April 2015, there are 60 sites open in 6 countries with 90 patients randomized. The study continues to enroll patients.
Results:
not applicable
Conclusion:
not applicable
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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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P3.01-003 - Patterns of Disease Progression for Stage IV NSCLC While on PD-1 Directed Therapy as Compared to Standard Chemotherapy (ID 3052)
09:30 - 09:30 | Author(s): T.K. Owonikoko
- Abstract
Background:
Programmed Cell Death 1 (PD-1) inhibitor therapy is now an established therapeutic modality in certain solid malignancies, including non-small cell lung cancer (NSCLC). The purpose of this study is to determine whether disease progression patterns are different between PD-1 inhibitor therapy or chemotherapy in patients with advanced NSCLC.
Methods:
We performed a retrospective analysis of patients who received PD-1 targeted therapies and systemic chemotherapy for advanced NSCLC treated at the Winship Cancer Institute at Emory University. We reviewed demographic data and treatment history of these patients. RECIST criteria were used to evaluate the patients’ baseline tumor burden and their subsequent disease progression from imaging studies (CT, PET/CT, MRI).
Results:
The total cohort included 37 patients with a mean age of 67 years. The PD-1 therapy group included 19 patients (14 males, 5 females), with 9 on MK-3475, 3 on MDPL3280A, and 7 on nivolumab. This group included 3 African Americans and 16 Caucasians. The median number of lines of prior chemotherapy was 3. A comparator group of 18 patients on standard chemotherapy was identified (14 males, 4 females). This group included 8 African Americans and 10 Caucasians. In the PD-1 therapy group, 5 patients had no progression and 14 had disease progression. Of these, 5 progressed at their sites of known cancer (36%), 4 progressed at new sites (28.5%), and 5 progressed at both old and new sites (36%). In the chemotherapy group, 4 patients had no disease progression and 14 had progression. Of those 14, 2 were at old sites only (14%), 4 were at new sites only (29%), and 8 were at both old and new sites (57%). The median time to progression was 3.5 months with PD-1 targeted therapy (range 2-13 months) and 6 months with chemotherapy (range 2-21 months).
Conclusion:
Our data suggests no difference between the progression patterns between PD-1 inhibitor therapy and standard chemotherapy patients. Patients on PD-1 therapy appear to have a shorter time to progression than those on traditional chemotherapy.
