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M. Redman
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MA11 - Novel Approaches in SCLC and Neuroendocrine Tumors (ID 391)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:P. Lara, A. Mohn-Staudner
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 3
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MA11.06 - SWOG 0124: Platinum-Sensitivity Status and Post-Progression Survival in Patients with Extensive-Stage Small Cell Lung Cancer (ID 3974)
14:56 - 15:02 | Author(s): M. Redman
- Abstract
- Presentation
Background:
Patients with extensive stage small cell lung cancer (ES-SCLC) who progress after frontline platinum-based chemotherapy are often considered “platinum-sensitive” (progression ≥ 90 days from last platinum dose) or “platinum-refractory” (progression < 90 days), as each group reportedly has differential overall survival (OS) outcomes. In a pooled analysis of recent SWOG trials of second and/or third-line targeted therapy, we showed that platinum-sensitivity status may no longer be as strongly associated with OS (Lara et al, JTO 2015). We assessed post-progression survival (PPS) following frontline platinum-based therapy in the context of platinum sensitivity status in ES-SCLC patients treated on SWOG 0124, a phase III trial of Irinotecan/Cisplatin vs Etoposide/Cisplatin.
Methods:
Data from 657 patients enrolled in S0124 were pooled. PPS was calculated as OS from the reported progression date. Crude PPS was evaluated according to platinum-sensitivity status. Hazard ratios (HRs) for PPS accounting for platinum-sensitivity and baseline clinical covariates (i.e., measured at the time of first line therapy) were calculated using single and multivariable Cox Proportional Hazard models. Baseline covariates were included in a logistic regression model to identify predictors of platinum-sensitivity. Recursive partitioning analysis (RPA) was performed to define prognostic risk groups.
Results:
Of 657 patients, 534 had a progression date and thus included in the analysis: 162 (25%) were platinum-sensitive and 372 (75%) refractory. Fewer patients with PS 0 (32% vs. 41%) and more patients with weight loss > 5% (40% vs. 31%) were seen in the refractory group. Crude unadjusted PPS was higher in platinum-sensitive vs refractory patients (median PPS 7.5 vs. 4.3 months; HR=1.64, p <0.001, 95%CI 1.356, 1.981). A multivariable Cox model showed that baseline elevated serum lactate dehydrogenase (LDH; HR=0.66, p<0.001) and platinum-sensitivity status (HR=1.54, p<0.001) were independently associated with PPS. None of the baseline covariates predicted for platinum-sensitivity. Prognostic groups with differential PPS based on platinum-sensitivity status, gender, and LDH were identified by RPA.
Conclusion:
PPS was significantly higher for S0124 patients categorized as platinum-sensitive vs. refractory. Limitations of this work include lack of relevant clinical data at the time of progression and number and type of post-progression therapies. These data have implications for the development of ES-SCLC trials in the salvage setting. [Supported by NIH/NCI/NCTN grants to SWOG: CA180888, CA180819, and in part by Pharmacia & Upjohn, a subsidiary of Pfizer. ClinicalTrials.gov Identifier: NCT00045162]
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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:G. Purkalne, J. Von Pawel
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 2
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MA16.10 - Lung-MAP (S1400) Lung Master Protocol: Accrual and Genomic Screening Updates (ID 3995)
15:20 - 15:26 | Author(s): M. Redman
- Abstract
- Presentation
Background:
Lung-MAP (S1400), is a master protocol that incorporates genomic testing of tumors through a next generation sequencing (NGS) platform (Foundation Medicine) and biomarker-driven (matched) therapies for patients with squamous cell lung cancer (SCCA) after progression on first-line chemotherapy.
Methods:
The Lung-MAP trial, activated June 16, 2014, includes 3 matched- and 1 non-match study. Matched studies include: S1400B evaluating taselisib, a PI3K inhibitor, S1400C evaluating palbociclib, a CDK 4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The non-match study S1400I tests nivolumab + ipilimumab vs. nivolumab. Two studies have closed: S1400E evaluating rilotumumab an HGF monoclonal antibody + erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match pts, closed 12/18/2015.
Results:
From June 16, 2014 to June 15, 2016, 812 pts were screened and 292 pts registered to a study: 116 to S1400A, 27 to S1400B, 53 to S1400C, 32 to S1400D, 9 to S1400E and 55 to S1400I. Demographics: Screening was successful for 705 (87%) of screened eligible pts. Median age 67 (range 35-92); male 68%; ECOG PS 0-1 88%, PS 2 10%; Caucasian 85%, Black 9%, other 5%; never/former/current smokers 4%/58%/36%. Table 1 displays biomarker prevalence; 39% of pts matched; 33.9%, 4.8%, and 0.3% with 1, 2, and all 3 biomarkers, respectively. Tumor mutation burden (TMB) was available for 636 (90.4%) of eligible pts. The distribution of TMB is: 126 (19.8%) low (≤5 mutations Mb), 415 (65.1%) intermediate (6-19 mutations/Mb), and 96 (15.1%) high (≥20 mutations/Mb). The median TMB was 10.1.
Conclusion:
Genomic screening is feasible as part of this master protocol designed to expedite drug registration, confirm anticipated prevalence of targeted alterations in SCCA and reveal intermediate or high TMB in most (80.2%) pts. Treatment results are not yet available as patients continue to accrue. Clinical trial information: NCT02154490Total FGFR CDK PIK3CA FGFR (15.9%) 12.9% 2.4% 0.6% CDK (18.8%) 14.6% 1.8% PIK3CA (8.8%) 6.4% Biomarker prevalence and overlap.
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P2.03b - Poster Session with Presenters Present (ID 465)
- 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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P2.03b-053 - Role of KRAS Mutation Status in NSCLC Patients Treated on SWOG S0819, a Phase III Trial of Chemotherapy with or without Cetuximab (ID 6113)
14:30 - 14:30 | Author(s): M. Redman
- Abstract
Background:
The S0819 phase III study of chemotherapy and bevacizumab (by patient/physician choice) with or without cetuximab in NSCLC showed no benefit from the addition of cetuximab, either overall or within the EGFR FISH-positive subset. Secondary analysis suggested an overall survival benefit in EGFR FISH-positive squamous cell carcinoma (SCC) (Herbst WCLC 2015, Hirsch ASCO 2016). In colorectal cancer (CRC), benefit from EGFR monoclonal antibodies such as cetuximab is limited to patients with RAS wild type (WT) tumors; however, in NSCLC, previous studies have not been sufficiently powered to make this determination. We prospectively incorporated KRAS mutation testing in S0819 to determine whether it predicts cetuximab efficacy. Since KRAS mutations are rare in SCC, we focused this analysis on nonSCC.
Methods:
KRAS mutation status was determined using the Therascreen KRAS test (Qiagen), conducted in a CLIA-certified diagnostic laboratory at the UC Davis Comprehensive Cancer Center. This test is FDA-approved for KRAS diagnostics in metastatic CRC, and identifies 6 mutations at codon 12 (G12A,D,R,C,S,V) plus G13D.
Results:
KRAS mutation status was available for 448 nonSCC patients, and mutations were identified in 150 cases (33%). Amino acid substitutions matched the expected distribution for a NSCLC population, with 52% harboring G12C and 17% with G12V. No significant differences were observed between KRAS-mut and WT populations for PFS (HR=1.15 (0.94-1.42); p=0.18) or OS HR=1.10 (0.89-1.37); p=0.39). Furthermore, no differences in outcomes between arms were observed based on KRAS mutation status (Table). The KRAS WT, EGFR FISH+ molecular subset (hypothetically the most likely subgroup to benefit from cetuximab) showed no statistical differences in outcomes between arms. Figure 1
Conclusion:
Determination of KRAS mutation status did not identify a subgroup of nonSCC patients with differential outcome from addition of cetuximab to front-line chemotherapy. In contrast to CRC, cetuximab does not appear to confer benefit to patients with KRAS-WT nonSCC NSCLC.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-052 - Afatinib with or without Cetuximab for First-Line Treatment of EGFR-Mutant NSCLC: Interim Safety Results of SWOG S1403 (ID 5798)
14:30 - 14:30 | Author(s): M. Redman
- Abstract
Background:
Afatinib is used as first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC), however resistance invariably develops. To attempt to delay resistance and improve survival, we are conducting a randomized Phase II/III trial of afatinib plus cetuximab versus afatinib alone in treatment-naïve patients with advanced EGFR-mutant NSCLC (NCT02438722).
Methods:
Previously untreated patients with EGFR exon 19 deletion or L858R point mutation are randomized to afatinib 40mg PO daily plus cetuximab 500mg/m2 IV every 2 weeks (afat/cetux) or afatinib 40mg PO daily (afat). Dose reductions are performed for grade 3-4 or intolerable or medically concerning grade 2 adverse events (AEs) per CTCAE v4.0. The Phase II primary endpoint is progression-free survival and the Phase III primary endpoint is overall survival. Here we review the safety data after enrollment of the first 53 patients.
Results:
53 patients were registered as of June 30, 2016, and safety has been assessed in 47 (23 treated with afat/cetux and 24 with afat, see Table). Grade 1-2 rash occurred in 71% of patients receiving afat/cetux and 63% of patients on afat. Grade 3 rash was noted in 22% of patients on afat/cetux. Fatigue was more common in the combination arm; all occurrences were grade 1-2. Grade 1-2 diarrhea and other gastrointestinal AEs were comparable between the two arms. There were similar numbers of dose reductions for AEs on each arm. Three patients discontinued treatment due to AEs: 2 on the afat/cetux arm due to hyperglycemia and accumulated side effects and 1 on the afat arm due to weight loss and diarrhea. Figure 1
Conclusion:
In this randomized trial of afat/cetux versus afat, treatment was tolerable in both arms of the study. Skin toxicity appears to be worse with the combination however other AEs are similar between the two groups. Enrollment to this trial is ongoing.
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SC28 - Novel Clinical Trial Designs (ID 352)
- Event: WCLC 2016
- Type: Science Session
- Track: Trial Design/Statistics
- Presentations: 1
- Moderators:S. Michiels, L.R. Pilz
- Coordinates: 12/07/2016, 11:00 - 12:30, Lehar 1-2
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SC28.03 - Biomarker “Test and Validation” Designs (ID 6719)
11:40 - 12:00 | Author(s): M. Redman
- Abstract
- Presentation
Abstract not provided
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