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B. Glisson
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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): B. Glisson
- 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.
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PL03 - Presidential Symposium Including Top Rated Abstracts (ID 85)
- Event: WCLC 2013
- Type: Plenary Session
- Track:
- Presentations: 1
- Moderators:M. Boyer, K. Fong
- Coordinates: 10/29/2013, 08:15 - 09:45, Plenary Hall, Ground Level
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PL03.07 - Treatment with Therapies Matched to Oncogenic Drivers Improves Survival in Patients with Lung Cancers: Results from The Lung Cancer Mutation Consortium (LCMC) (ID 2444)
08:15 - 09:45 | Author(s): B. Glisson
- Abstract
Background
Detecting and targeting the oncogenic drivers EGFR and ALK have transformed the care of patients with lung adenocarcinomas. The LCMC was established to use multiplexed assays to test tumors for alterations in 10 genes and provide the results to clinicians to select treatments and clinical trials matched to the driver detected.Methods
Fourteen LCMC sites enrolled patients with metastatic lung adenocarcinomas and tested their tumors in CLIA laboratories for activating mutations in 10 oncogenic driver genes.Results
Tumors were tested from 1,007 patients for at least one gene and 733 for all 10 genes. An oncogenic driver was found in 466 (64%) of fully-genotyped cases. Among these 733 tumors, drivers found were: KRAS 182 (25%), sensitizing EGFR 122 (17%), ALK rearrangements 57 (8%), “other” EGFR 29 (4%), two genes 24 (3%), HER2 19 (3%), BRAF 16 (2%), PIK3CA 6 (1%), MET amplification 5 (1%), NRAS 5 (1%), MEK1 1 (<1%), AKT1 0. For cases with any genotyping, we used results to select a targeted therapy or trial in 275 (28%). Among 938 patients with follow-up, the median survivals were 3.5 years for the 264 with an oncogenic driver treated with genotype-directed therapy, 2.4 years for the 318 with an oncogenic driver with no genotype-directed therapy, and 2.1 years for the 360 with no driver identified (p<0.0001).Conclusion
Individuals with lung cancers with oncogenic drivers receiving a corresponding targeted agent lived longer than similar patients who did not. An actionable driver was detected in 64% of tumors from patients with lung adenocarcinomas; more than one was present in 3%. Multiplexed testing aided physicians in choosing therapies and targeted trials in 28% of patients. This paradigm for care and research will expand as genotyping becomes more efficient with Next-Gen platforms, additional drivers are identified (i.e.ROS1 and RET), and more targeted drugs become available in the pharmacy and through clinical trials. Supported by HSS NIH NCI 1RC2CA148394-01. Trial Registered with Clinicaltrials.gov: NCT01014286.
