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R.N. Pillai
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.05 - Nivolumab Alone or with Ipilimumab in Recurrent Small Cell Lung Cancer (SCLC): 2-Year Survival and Updated Analyses from the Checkmate 032 Trial (ID 4397)
14:50 - 14:56 | Author(s): R.N. Pillai
- Abstract
- Presentation
Background:
Patients with SCLC and disease progression during/after first-line platinum-based chemotherapy have poor prognoses and limited treatment options. Nivolumab alone and in combination with ipilimumab has shown survival benefit and durable responses in multiple tumor types. Here we present updated results for the SCLC cohort of the phase 1/2 CheckMate 032 trial (NCT01928394), which was designed to evaluate nivolumab or nivolumab/ipilimumab in advanced solid tumors.
Methods:
Patients with advanced SCLC that progressed following ≥1 platinum-based chemotherapy regimens were assigned to receive nivolumab monotherapy (nivolumab-3 Q2W) or nivolumab/ipilimumab combination therapy (nivolumab-1/ipilimumab-3 or nivolumab-3/ipilimumab-1 Q3W for 4 cycles, then nivolumab-3 Q2W). Patients were eligible regardless of platinum sensitivity or tumor programmed death ligand 1 (PD-L1) expression. The primary endpoint was ORR. Additional endpoints were duration of response (DOR), OS, PFS, safety, and correlation of tumor PD-L1 expression with activity.
Results:
214 patients have been enrolled to date (nivolumab-3, n=98; nivolumab-1/ipilimumab-3, n=61; nivolumab-3/ipilimumab-1, n=55), including 96 and 118 patients treated with 1 or ≥2 prior regimens, respectively. Efficacy and safety data are shown (table). In the nivolumab-1/ipilimumab-3 cohort, ORR was 23% and 1-year OS was 43%. The proportion of patients with PD-L1–expressing tumors was substantially lower in previously treated SCLC in this study than that previously observed with pretreated NSCLC (16% vs 53%–54% with ≥1% PD-L1 expression). In SCLC, responses were observed regardless of PD-L1 expression. ORR and median OS were similar in patients treated with 1 or ≥2 prior regimens. Rate of discontinuation due to treatment-related AEs ranged from 5% to 11%; there were 3 treatment-related deaths. Figure 1
Conclusion:
Durable objective responses were observed with nivolumab and nivolumab/ipilimumab in patients with previously treated SCLC, and safety profiles were consistent with other tumor types. Updated efficacy (including 2-year OS and DOR), safety, and additional subgroup analyses will be presented from the August 2016 DBL.
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
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OA03.06 - Evaluation of Toxicity Profile of PD-1 versus PD-L1 Inhibitors in Non-Small Cell Lung Cancer (NSCLC) (ID 6073)
11:55 - 12:05 | Author(s): R.N. Pillai
- Abstract
- Presentation
Background:
Monoclonal antibodies against Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1) have emerged as effective therapies in NSCLC. We updated our initial systematic review of trials investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.
Methods:
An electronic literature search was performed of public databases (MEDLINE, EMBASE) and conference proceedings for trials utilizing PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, avelumab) in NSCLC patients. Studies that did not report toxicities were excluded. A formal meta-analysis was conducted with Comprehensive Meta-Analysis software (Version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between the two groups.
Results:
Twenty-two studies reported between 2013-2016 were eligible for this analysis. The total number of patients evaluated for toxicities were 2,863 patients in the PD-1 group and 2,006 patients in the PD-L1 group. Patient characteristics % (PD-1/PD-L1): median age 64/65, male 58/56, smokers 82/83, squamous histology 25/32, performance status 0-1 98/100. There was no difference in response rate between PD-1 (17%) and PD-L1 (18%) inhibitors, p=0.3. The incidence of overall adverse events (AEs), immune related AEs, and pneumonitis trended in favor of the PD-L1 group but did not reach statistical significance (see table). Figure 1
Conclusion:
In this updated systematic review involving 4,869 patients, the toxicity profiles of PD-1 and PD-L1 inhibitors in NSCLC patients are not significantly different.
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P1.01 - Poster Session with Presenters Present (ID 453)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.01-035 - Trends, Patterns of Treatment and Outcomes in Non-Small Cell Lung Cancer (NSCLC) as a Second Primary: A National Cancer Data Base (NCDB) Analysis (ID 6185)
14:30 - 14:30 | Author(s): R.N. Pillai
- Abstract
Background:
The prevalence of NSCLC as a second primary tumor has been increasing over the past decades, though very little data are available in the literature. We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the outcomes and patterns of treatment of patients (pts) diagnosed with NSCLC as a second or subsequent primary (SP).
Methods:
The NCDB was queried from 2004 to 2012 for NSCLC pts. Pts diagnosed with NSCLC as SP were compared with pts with de novo (DN) NSCLC as defined by sequence number in the database. Univariate (UV) and multivariable analyses (MV) with overall survival (OS) were conducted by Cox proportional hazards model. Kaplan-Meier plots were produced to compare the survival curves by subgroups along with log-rank p-values.
Results:
A total of 207,518 pts in SP and 697,709 pts in DN groups were included in the analysis, which accounted for 22% and 74% of all NSCLC pts respectively. Pt characteristics (SP/DN %): median age 72/68, male 53/53, white 89/84, stage IV 28/41, treated at academic centers 33/32, government insured 72/57, mean tumor size (cm) 3.5/4.4. An increasing trend in incidence of SP was observed (19.5% in 2004 to 24% in 2012) vs. a decreasing trend in DN (75.6% in 2004 to 73% in 2012). About 12% in SP and 15% in DN received chemotherapy as part of their treatment. Surgery was performed in 39% of SP group vs. 28% in DN. Radiation was given to 43% of the pts in DN vs. 36% in SP. On UV and MV analysis, SP was associated with better survival than DN (HRs 0.84 and 0.93 respectively; p<0.001). The SP group had higher 5-year OS (23% vs. 19.6%, p<0.001) and a higher median survival (17 vs. 11.5 months) compared to DN. On stratifying by stage, DN had inferior survival in stage IV pts (HR 1.12, p<0.001) compared to SP but better survival in stage I and II pts (HRs 0.86 and 0.93, p<0.001). No difference in OS was seen in stage III pts (HR 1.01, p= 0.4).
Conclusion:
The incidence of second primary has increased over the past decade. Second primary NSCLC is diagnosed at an earlier stage, smaller tumor size, and is associated with a better survival, compared to de novo NSCLC.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-014 - Impact of Chemotherapy for Small Cell Lung Cancer in the Third Line and beyond, a SEER-MEDICARE Analysis (ID 4758)
14:30 - 14:30 | Author(s): R.N. Pillai
- Abstract
Background:
While there is no approved third line chemotherapy option for small cell lung cancer (SCLC), empiric use of chemotherapy is common in this setting in the absence of supporting prospective data. In order to assess the potential benefit and predictors of chemotherapy use beyond the second line setting in SCLC, we analyzed the SEER-MEDICARE database.
Methods:
We employed data of SCLC patients diagnosed between 1985 and 2005. Univariate (UVA) association of line of chemotherapies with covariates was examined with Wilcoxon rank-sum test, chi-square or Fisher’s exact test. Multivariable (MVA) logistic regression analysis for line of therapy was conducted using the following covariates: year of diagnosis, age, gender, race, Medicare status, urban/rural location, and radiation. Survival functions were estimated by the Kaplan-Meier method and the log-rank test was used to assess for difference in overall survival (OS) stratified by line of therapy. UVA and MVA survival analyses were carried out using the Cox proportional hazards model. To further balance confounders between patients receiving different lines of therapy, propensity scores were estimated using a MVA logistic regression model to predict the receipt of 3[rd] line chemotherapy based on relevant covariates. Propensity score analysis was further conducted by including the estimated propensity score as a covariate in a Cox proportional hazards model. All analyses were done using SAS 9.3 with two-sided tests and a significant level of 0.05.
Results:
There were 47,351 patients with SCLC of which 23,535 (49.7 %) received chemotherapy and 10,887 (23%) received platinum-based chemotherapy. Of the platinum-treated patients, 1424 (13.1%) received additional salvage therapy of either topotecan alone (n=801) or topotecan and additional treatments as 3[rd] line and beyond (n=623). The median OS was 11, 13, 15 and 17 months respectively for patients treated with one, two, three or > 3 lines of chemotherapy respectively. Propensity score analysis showed additional lines of therapy beyond the second line was associated with a reduced risk of death (HR: 0.786; 0.729 - 0.847, p<0.001 and 0.617; 0.564 - 0.675; p<0.001 for 3[rd] line and > 3 lines of therapy respectively). Age (p=0.043) and year of diagnosis (P<0.001) were significantly associated with treatment beyond 2[nd] line topotecan on MVA analysis.
Conclusion:
Salvage chemotherapy is not commonly used following failure of platinum containing chemotherapy in SCLC patients. However, chemotherapy beyond the second line was associated with an incremental survival benefit in US MEDICARE-eligible SCLC patients.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-015 - Guideline Concordant Care is Associated with Better Survival for Patients with Stage III Non-Small Cell Lung Cancer (ID 5103)
14:30 - 14:30 | Author(s): R.N. Pillai
- Abstract
Background:
Current evidence-based guideline-concordant care (GCC) is administration of platinum-based chemotherapy during thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (NSCLC) patients with good performance status. This study evaluates factors associated with lack of GCC.
Methods:
Patients (pts) with unresected stage IIIA/IIIB NSCLC diagnosed from 2005 – 2013 and Charlson-Deyo Score 0 were identified from the National Cancer Data Base (NCDB). Primary outcomes measured were receipt of GCC, defined by administration of chemotherapy with TRT commencing within 2 weeks of each other and minimum TRT dose of 60 Gy, and overall survival (OS). Multivariable logistic regression (MLR) modeling was performed to identify variables associated with non-GCC. Cox proportional hazard modeling was utilized to examine OS.
Results:
Patient characteristics (n=37,809) included: mean age 67.8 years; 55% male; 13% African American; 3.4% Hispanic, 3.6% ‘other’ race/ethnicity; 66% government-insured; mean tumor size 5.0 cm; 38% adenocarcinoma; 32% squamous cell carcinoma (SCC); 30% large cell/other histology. In total, 28% of pts received GCC. On MLR analysis, Hispanic pts were more likely to receive non-GCC (OR=1.34, p <0.001) compared to non-Hispanic pts. Uninsured pts were more likely to receive non-GCC (OR=1.57, p<0.001) compared to privately-insured pts. Patients treated in the western, southern, or northeastern U.S. were more likely to receive non-GCC (OR= 1.43, 1.45, 1.21, all p values <0.001) compared to pts treated in the Midwest. Adenocarcinoma and large-cell/other histological types were more likely to receive non-GCC (OR= 1.71, 1.39, both p<0.001) compared to SCC. For every one-year increase in age or 50-mile increase in distance to treatment facility, patients had a 4% or 3% increased odds of not receiving GCC (OR=1.04, 1.03; p<0.001, p = 0.003, respectively). On hazard modeling, those receiving non-GCC had higher death rates compared to those receiving GCC (HR=1.42, p<0.001). Survival rates were lower for Hispanics receiving non-GCC versus GCC (HR=1.24, p=0.034). Other groups with lower OS for non-GCC versus GCC included: the uninsured (HR=1.61, p<0.001), treatment in the western, southern, or northeastern US (HRs= 1.56, 1.40, 1.33, respectively, p<0.001), adenocarcinomas and large cell/other histologies (both HR=1.40, p<0.001).
Conclusion:
Socioeconomic factors, including Hispanic ethnicity, lack of insurance, geographic location, and distance from treatment facility are associated with receipt of non-GCC. Patient and disease specific factors including increasing age and adenocarcinoma histology are also associated with non-GCC. Future interventions could target these groups to improve provision of GCC.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-049 - Response to Salvage Chemotherapy Following Exposure to PD-1 Inhibitors in Patients with Non-Small Cell Lung Cancer (ID 6277)
14:30 - 14:30 | Author(s): R.N. Pillai
- Abstract
Background:
Programmed death-1 (PD-1) inhibitors are effective second line treatment in non-small cell lung cancer (NSCLC), however objective responses are seen in only 20-30% of patients. While a minority of patients achieve durable response to PD-1 inhibitors, those who progress or are refractory receive salvage chemotherapy. We evaluate response to salvage chemotherapy following exposure to PD-1 inhibitors.
Methods:
Eligible patients were adults with NSCLC followed at the Vanderbilt Cancer Center or the Winship Cancer Institute from 2011 to 2016 who received salvage chemotherapy following PD-1 inhibitors (cases) versus no PD-1 inhibitors (controls). CT-imaging of the chest/abdomen/pelvis was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response to treatment. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response.
Results:
Three hundred patients’ charts were reviewed and 56 patients met eligibility criteria. Among evaluable patients, 28 were males versus 28 females. Median age was 61.64 years (interquartile ranges (IQR): 55.33–69.36) in cases versus 67.82 (IQR: 54.08-72.24) in controls. Forty-one patients were classified as cases versus 15 controls. Thirty-six patients received nivolumab and 5 pembrolizumab. Forty-five (80%) patients had adenocarcinoma, 10 (18%) squamous cell carcinoma and 1 (2%) large cell carcinoma. The median number of chemotherapy regimens prior to salvage chemotherapy was 3 (IQR: 2-3) in cases versus 2 (IQR: 1-2) in control. The drugs most commonly used in salvage regimens included docetaxel, pemetrexed, paclitaxel, gemcitabine. Seven (17%) cases had partial response to chemotherapy versus 1(6.6%) controls. Eleven (27%) cases had progressive disease versus 6 (40%) controls. Twenty-three (56%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.16 (95% CI: 0.08 to 0.35, P=0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response.
Conclusion:
The odds of achieving a partial response to salvage chemotherapy were 6 times higher in patients with prior exposure to PD-1 inhibitors. This observed difference however warrants confirmation in larger cohorts. If confirmed, this difference may represent an argument to promote immune PD-1 inhibitors as first line regimen for the treatment of NSCLC not amenable to targeted therapy.
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PL03 - Presidential Symposium (ID 428)
- Event: WCLC 2016
- Type: Plenary
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, R. Pirker
- Coordinates: 12/06/2016, 08:35 - 10:25, Hall D (Plenary Hall)
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PL03.09 - Phase 3 Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, with Docetaxel versus Docetaxel in Advanced Non-Small Cell Lung Cancer (GALAXY-2) (Abstract under Embargo until December 6, 7:00 CET) (ID 5232)
10:05 - 10:15 | Author(s): R.N. Pillai
- Abstract
- Presentation
Background:
Heat shock protein 90 functions as a chaperone to stabilize oncoproteins. Ganetespib (G), a highly potent Hsp90 inhibitor, has demonstrated efficacy in combination with docetaxel (D) over D alone in the second-line therapy of patients with advanced adenocarcinoma of the lung in a phase 2 study.
Methods:
GALAXY-2 is a randomized (1:1), international, open-label study of D with or without G. Patients with advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) of adenocarcinoma histology, EGFR and ALK wild-type, diagnosed ≥ 6 months prior to study entry, one prior systemic therapy and ECOG PS 0-1 were eligible. D was given at 75 mg/m[2] on day 1 of three-week cycle; D was given on day 1 with G at 150 mg/m[2 ]on Days 1 and 15 of each cycle. Patients were stratified by performance status (PS), LDH, and geographic region. Primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and OS in elevated LDH (eLDH) patients. We report the results of a planned interim analysis at 336 events, which occurred on October 5, 2015, with type I error level set at 0.01 (2 sided stratified log-rank test).
Results:
677 patients were randomized with 335 patients in G+D arm and 337 patients in D arm. Baseline characteristics: females 60%, age < 65 68%; never-smoker 18%; PS 0 36%; eLDH 29%; North America/Western Europe 39%. The median number of cycles delivered was 5 in G+D and 4 in D arm. There was no difference in median OS (mOS) for the two arms: 10.9 months with G+D versus 10.5 months with D alone. The hazard ratio for OS was 1.111 (95% CI 0.899-1.372), which met the early stopping criteria for futility. Median PFS was similar in the two arms: 4.2 versus 4.3 months, G+D and D, respectively (HR 1.161, 95% CI 0.961-1.403). There was no improvement with the addition of G for any secondary endpoint, including survival in the eLDH and EGFR and ALK negative populations, response rate, or progression due to new metastatic lesions. The most common grade 3/4 treatment-emergent adverse event in both arms was neutropenia (31.1% versus 24.3%, G+D and D, respectively).
Conclusion:
The addition of ganetespib to docetaxel did not result in improved efficacy for salvage therapy of patients with advanced stage lung adenocarcinoma.
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