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M. Kowanetz
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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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OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study (ID 4799)
11:10 - 11:20 | Author(s): M. Kowanetz
- Abstract
- Presentation
Background:
Atezolizumab, a humanized anti-PDL1 mAb, inhibits the PD-L1/PD-1 pathway to restore tumor-specific T-cell immunity, resulting in durable anti-tumor effects. BIRCH (NCT02031458) is a single-arm Phase II study of atezolizumab monotherapy in PD-L1–selected advanced NSCLC patients, across multiple therapy lines. Primary analyses (median follow-up, 8.5 months) demonstrated a meaningful ORR with durable response in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we report updated efficacy data in 1L patients.
Methods:
1L eligibility criteria included PD-L1–selected, advanced-stage NSCLC with no CNS metastases or prior chemotherapy. PD-L1 was centrally evaluated (VENTANA SP142 IHC assay). Patients expressing PD-L1 on ≥5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3, were enrolled. Patients with EGFR mutation or ALK rearrangement must have had prior TKI treatment. Atezolizumab 1200mg was administered IV q3w until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility(IRF)-assessed ORR. Secondary endpoints included investigator(INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.
Results:
With a median follow-up of 14.6 months, median OS was not reached in TC3 or IC3 patients and was 20.1 months in TC2/3 or IC2/3 (ITT) patients; INV-assessed ORR was 32% and 24%, respectively (Table). Furthermore, ORR was 31% for mutant EGFR (n=13) vs 20% for wild-type EGFR patients (n=104), and 27% for mutant KRAS (n=33) vs 21% for wild-type KRAS patients (n=67). No new safety signals were observed. Updated efficacy (including IRF ORR), safety and exploratory biomarker analyses will be presented.
Conclusion:
With longer follow-up, atezolizumab continued to demonstrate promising efficacy in 1L NSCLC. These results indicate that atezolizumab has durable efficacy in the 1L setting, in EGFR and KRAS mutant and wild-type tumors, and support ongoing Phase III trials evaluating atezolizumab vs chemotherapy in 1L NSCLC.
NE, not estimable.[a ]TC ≥50% or IC ≥10% PD-L1–expressing cells.[b ]TC or IC ≥5% PD-L1–expressing cells.Endpoint(95% CI) TC3 or IC3[a](n=65) TC2/3 or IC2/3[b](n=139) INV ORR, % 32% (21.2–45.1) 24% (16.9–31.7) EGFR mutant/wild-type, % 25%/29% 31%/20% KRAS mutant/wild-type, % 38%/27% 27%/21% mDOR, mo 13.1 (8.5–NE) 13.1 (9.9–17.5) mOS, mo NE (12.0–NE) 20.1 (20.1–NE) 12-mo OS rate, % 61% (48.8–73.8) 66% (57.9–74.5) mPFS, mo 7.3 (4.9–12.0) 7.3 (5.6–9.1) 12-mo PFS rate, % 36% (23.8–48.8) 32% (24.0–40.7)
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PL04a - Plenary Session: Immune Checkpoint Inhibitors in Advanced NSCLC (ID 430)
- Event: WCLC 2016
- Type: Plenary
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:J. Soria, C. Zhou
- Coordinates: 12/07/2016, 08:45 - 09:40, Hall D (Plenary Hall)
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PL04a.02 - OAK, a Randomized Ph III Study of Atezolizumab vs Docetaxel in Patients with Advanced NSCLC: Results from Subgroup Analyses (Abstract under Embargo until December 7, 7:00 CET) (ID 5822)
08:55 - 09:05 | Author(s): M. Kowanetz
- Abstract
- Presentation
Background:
Atezolizumab inhibits PD-L1 binding to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. Primary analysis of the Phase III OAK study in previously-treated NSCLC revealed superior survival for atezolizumab vs docetaxel in the ITT population (mOS, 13.8 vs 9.6 months; HR, 0.73) and in patients expressing ≥1% PD-L1 on TC or IC (TC1/2/3 or IC1/2/3; mOS, 15.7 vs 10.3; HR, 0.74). Here we present further subgroup analyses.
Methods:
OAK evaluated atezolizumab vs docetaxel in an unselected NSCLC population who had failed prior platinum-containing chemotherapy. Patients were stratified by PD-L1 expression, prior chemotherapy regimens and histology, and randomized 1:1 to atezolizumab (1200 mg) or docetaxel (75 mg/m[2]) IV q3w. PD-L1 expression by IHC and mRNA was centrally evaluated by VENTANA SP142 IHC assay and Fluidigm, respectively. Data cutoff, July 7, 2016.
Results:
For the first 850 of 1225 randomized patients (primary study population), OS was improved with atezolizumab vs docetaxel regardless of histology and this benefit was observed across PD-L1 subgroups within each histology (Table). PD-L1 gene expression showed a similar association with OS as PD-L1 IHC. In nonsquamous patients ORR was 14.4% vs 15.2%; in squamous patients ORR was 11.6% vs 8.2% (atezolizumab vs docetaxel). OS benefit vs docetaxel was seen across subgroups including patients with treated baseline brain metastases (n=85; mOS 20.1 vs 11.9 mo; HR 0.54, 95% CI 0.63-0.89) and never smokers (n=156; mOS 16.3 vs 12.6 mo, HR 0.71, 95% CI 0.47-1.08). Further secondary endpoints and exploratory biomarker analyses for these subgroups and by age and EGFR/KRAS status will be presented.
Conclusion:
OAK demonstrated clinically relevant improvements with atezolizumab in the ITT population, including in both histology subgroups regardless of PD-L1 expression (measured by IHC or tumor gene expression), and among other subgroups including never smokers and in patients with baseline brain metastases.OS Atezolizumab Docetaxel HR[a]95% CI n Median, mo n Median, mo Nonsquamous TC3 or IC3 49 22.5 47 8.7 0.35(0.21-0.61) TC2/3 or IC2/3 89 18.7 99 11.3 0.61(0.42-0.88) TC1/2/3 or IC1/2/3 171 17.6 162 11.3 0.72(0.55-0.95) TC0 and IC0 140 14.0 150 11.2 0.75(0.57-1.00) All 313 15.6 315 11.2 0.73(0.60-0.89) Squamous TC3 or IC3 23 17.5 18 11.6 0.57(0.27-1.20) TC2/3 or IC2/3 40 10.4 37 9.7 0.76(0.45-1.29) TC1/2/3 or IC1/2/3 70 9.9 60 8.7 0.71(0.48-1.06) TC0 and IC0 40 7.6 49 7.1 0.82(0.51-1.32) All 112 8.9 110 7.7 0.73(0.54-0.98) [a]Unstratified HRs. TC=tumor cell, IC=tumor-infiltrating immune cell
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