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S. Orlov
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Best of Posters - IASLC Selection - Part 2 (ID 263)
- Event: WCLC 2013
- Type: Exhibit Showcase Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:55 - 10:25, Exhibit Hall, Ground Level
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P2.11-024 - Efficacy Analysis for Molecular Subgroups in MARQUEE: a Randomized, Double-blind, Placebo-controlled, Phase 3 Trial of Tivantinib (ARQ 197) Plus Erlotinib versus Placebo plus Erlotinib in Previously Treated Patients with Locally Advanced or Metastatic, Non-squamous, Non- small Cell Lung Cancer (NSCLC) (ID 2909)
09:55 - 10:25 | Author(s): S. Orlov
- Abstract
Background
MARQUEE, a Phase 3 study which investigated the role of tivantinib, a c-MET inhibitor, in previously treated non-squamous NSCLC, collected EGFR and KRAS genotype on >90% of randomized patients, and MET expression was determined for 42%. In the ITT population, addition of tivantinib to erlotinib significantly improved PFS and ORR but did not show benefit in OS. Additional efficacy analyses in the pre-defined molecular subgroups are presented.Methods
Patients with locally advanced or metastatic non-squamous, EGFR inhibitor naive NSCLC previously treated with 1 or 2 lines of systemic therapy, including a platinum-doublet, were stratified by number of prior therapies, sex, smoking history, and EGFR and KRAS mutation status, then randomized to oral tivantinib (360 mg twice daily) + erlotinib (150 mg once daily) or placebo + erlotinib until disease progression. Primary endpoint was OS with one interim analysis for futility/superiority. MET was assessed centrally by IHC using CONFIRM (SP44) antibody. Based upon a stability study, tumor tissue must have been sectioned within 90 days prior to MET immunostaining to be considered reliable. MET High was pre-specified as ≥50% of tumor cells staining with 2+ or 3+ intensity.Results
From 1/2011 to 7/2012, 1048 patients were randomized to tivantinib + erlotinib (TE, n=526) or placebo + erlotinib (PE, n=522). Baseline characteristics were median age = 62 years (range, 24-89), prior therapies = 1 (66%) or 2 (34%), ECOG performance status = 0 (32%) or 1 (68%), EGFR mutant (10.4%), and KRAS mutant (27.1%). In 9/2012, the data monitoring committee recommended trial discontinuation because the pre-planned interim analysis of OS crossed the futility boundary. At the 12/2012 data cutoff, median OS was 8.5 months and 7.8 months for TE and PE, respectively (hazard ratio [HR] = 0.98; 95% CI, 0.84-1.15; p = 0.81). Median PFS was 3.6 months and 1.9 months, respectively (HR = 0.74; 95% CI, 0.62-0.89; p < 0.0001). Overall response rate (ORR) improved to 10.3% for TE compared with 6.5% for PE (p < 0.05). MET expression was obtained for 445 patients. In the pre-specified, MET High subgroup (n = 211), median OS improved to 9.3 months for TE vs 5.9 months for PE (HR = 0.70; 95% CI, 0.49-1.01; p = 0.03). In the MET Low subgroup (n = 234), median OS was 8.5 months for TE and 7.7 months for PE (HR=.90, 95% CI, 0.64-1.26, p=.53). OS did not differ between treatments in KRAS wildtype (n=702), KRAS mutant (n=284), and EGFR wildtype (n=937) subgroups; OS was immature for the EGFR mutant (n=109) subgroup at the cut-off time. Consistent with ITT, PFS was increased with TE vs PE across all molecular subgroups. Common adverse events (TE vs PE, respectively) included rash (33.1% vs 37.3%), diarrhea (34.6% vs 41.0%), and asthenia/fatigue (43.5% vs 38.1%), which occurred at similar rates between treatments; neutropenia (Grade 3/4: 10.0% vs 1.0%) was more common with TE.Conclusion
Tivantinib significantly improved PFS and OS in the prospectively defined MET High subgroup. Further investigation of tivantinib in MET High selected, non-squamous NSCLC is warranted.
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O21 - SCLC II (ID 119)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:M. Ahn, P. Lara
- Coordinates: 10/29/2013, 16:15 - 17:45, Parkside Ballroom B, Level 1
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O21.05 - A multicenter, double-blind, placebo-controlled, randomized phase 2 study of ganitumab or rilotumumab with platinum-based chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) (ID 725)
16:15 - 17:45 | Author(s): S. Orlov
- Abstract
- Presentation
Background
The type 1 insulin-like growth factor receptor (IGF1R) and MET, the receptor for hepatocyte growth factor (HGF)/scatter factor, appear to play key roles in SCLC. Ganitumab and rilotumumab are investigational, fully human monoclonal antibodies targeting IGF1R and HGF, respectively. A phase 1b/2 study evaluated ganitumab or rilotumumab combined with etoposide plus carboplatin (CE) or cisplatin (PE) in extensive-stage SCLC. The phase 1b results were previously reported (Lorigan et al. Ann Oncol 2010;21[supplement 8]: abstract 444P). Here, the phase 2 results are reported.Methods
Key eligibility criteria: ≥18 years, confirmed SCLC, ECOG performance status ≤1, no prior chemotherapy. Patients were randomized 1:1:1 to receive blinded investigational product (IP) either ganitumab (18 mg/kg IV, day 1) or rilotumumab (15 mg/kg IV, day 1) or placebo, with etoposide (100 mg/m[2] IV, days 1-3) plus, at investigator’s discretion, either carboplatin (AUC=5 mg/mL*minute IV, day 1) or cisplatin (75 mg/m[2] IV, day 1) every three weeks for 4-6 cycles followed by IP monotherapy. Patients were stratified by gender and chemotherapy (CE; PE). Primary endpoint: overall survival (OS). Key secondary endpoints included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), pharmacokinetics.Results
185 patients (ganitumab/rilotumumab/placebo: 62/62/61) were enrolled between 2 February 2010 and 12 January 2011. Male: 77%/76%/77%. Median age: 60/61/61 years. More patients received carboplatin (41/40/40) than cisplatin (21/22/21). Most common reason for discontinuation of IP was disease progression (69%/61%/74%). Among 179 patients (59/61/59) who received IP, the most frequent any grade AEs (occurring in ≥30% of patients in any arm) were neutropenia (69%/59%/71%), anemia (39%/34%/36%), nausea (41%/30%/22%), alopecia (41%/23%/27%), thrombocytopenia (22%/30%/12%), and vomiting (19%/10%/31%). Grade ≥3 AEs and serious AEs were reported in 69%/72%/80% and 39%/38%/36% of patients, respectively. There were three IP-related grade 5 AEs: cardiac arrest (rilotumumab, n=1), febrile neutropenia (rilotumumab, n=1), gastric ulcer hemorrhage (placebo, n=1). No neutralizing antibodies were observed for either ganitumab or rilotumumab. Efficacy is shown in the table. Ganitumab and rilotumumab combined with chemotherapy showed comparable exposures as those under monotherapy and did not affect the pharmacokinetics of chemotherapy.
[a]Adjusted for baseline lactate dehydrogenase levels and stratification factors. CI=confidence interval; HR=hazard ratio.Ganitumab (n=62) Rilotumumab (n=62) Placebo (n=61) OS Median (95% CI) months 10.7 (8.1–14.1) 12.2 (8.8–14.6) 10.8 (9.4–11.9) Adjusted HR[a] (95% CI) 1.01 (0.67–1.52) 0.91 (0.60–1.39) PFS Median (95% CI) months 5.5 (4.4–5.7) 5.4 (4.4–5.7) 5.4 (4.6–5.8) Adjusted HR[a] (95% CI) 1.03 (0.70–1.52) 1.03 (0.69–1.52) Objective Response Complete response, n (%) 0 (0) 2 (3) 1 (2) Partial response, n (%) 39 (63) 40 (65) 35 (57) Stable disease, n (%) 13 (21) 12 (19) 16 (26) Conclusion
In this study of chemonaïve patients with extensive-stage SCLC, the combination of ganitumab or rilotumumab with CE or PE was tolerable; no unexpected toxicities were observed. There were no meaningful improvements in OS, PFS, or ORR with either combination. Survival analyses in biomarker and pharmacokinetic subgroups are ongoing.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
