84O - Atezolizumab as first-line (1L) therapy for advanced non-small cell lung cancer (NSCLC) in PD-L1–selected patients: Efficacy data from the BIRCH trial

Date 06 May 2017
Event ELCC 2017
Session Immunotherapies and targeted therapies in advanced NSCLC
Presenter Solange Peters
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors S. Peters1, E. Carcereny Costa2, M.C. Garassino3, D. Christoph4, T. Kurata5, J. Chaft6, M.L. Johnson7, S. Mocci8, S.N. Gettinger9, E. Felip10
  • 1HFR Fribourg-Hôpital Cantonal, 1011 - Fribourg/CH
  • 2Catalan Institute of Oncology Badalona—Germans Trias I Pujol Hospital Badalona, Barcelona/ES
  • 3Fondazione IRCCS Istituto Nazionale dei Tumori, Thoracic Oncology Unit, Milano/IT
  • 4West German Cancer Center, Universitätsklinikum Essen, and the Ruhrlandklinik, Universität Duisburg–Essen, Essen/DE
  • 5Kansai Medical University Hirakata Hospital, Osaka/JP
  • 6Memorial Sloan Kettering Cancer Center, New York/US
  • 7Sarah Cannon Research Institute, Nashville/US
  • 8Genentech, Inc., South San Francisco/US
  • 9Yale Cancer Center, New Haven/US
  • 10Vall d´Hebron Institute Oncology, Barcelona/ES

Abstract

Background

Atezolizumab (atezo) inhibits binding of PD-L1 to its receptors, PD-1 and B7.1, restoring tumor-specific T-cell immunity and leaving the PD-L2/PD-1 interaction intact. This single-arm Phase II study (BIRCH; NCT02031458) was designed to evaluate atezo monotherapy in PD-L1–selected patients with advanced NSCLC. A previous analysis (median follow-up, 8.5 months) demonstrated clinical activity in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we present updated efficacy data for 1L patients.

Methods

Eligible patients had PD-L1–selected advanced-stage NSCLC, with no prior chemotherapy or CNS metastases. PD-L1 was centrally evaluated using the VENTANA SP142 IHC assay. Enrolled patients expressed PD-L1 on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3. Those with EGFR mutation or ALK rearrangement must have had prior treatment with an appropriate TKI. Atezo was administered (1200 mg 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 duration of survival follow-up of 22.5 months, INV-assessed ORR was 25% in TC2/3 or IC2/3 (all treated) patients and 34% in TC3 or IC3 patients (Table). Median OS was 23.5 months in all treated patients and 26.9 months in the TC3 or IC3 subgroup. Responses were observed in both EGFR and KRAS mutant and wild-type tumors. The safety profile was consistent with previous atezo NSCLC studies.

Conclusions

With a median follow-up of 22.5 months, atezo continued to demonstrate durable clinical benefit in 1L NSCLC, in both EGFR and KRAS mutant and wild-type tumors. These results support ongoing Phase III trials evaluating atezo vs chemotherapy in 1L NSCLC.rnTable: 84Orn

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
Endpoint (95% CI)TC3 or IC3a (n = 65)TC2/3 or IC2/3b (n = 138)
INV ORR, %34%25%
(22.6-46.7)(18.4-33.5)
EGFR mutant/wild type, ORR, %25%/31%31%/22%
KRAS mutant/wild type, ORR, %38%/30%31%/22%
Median DOR, moNE16.5
(8.5-NE)(9.9-NE)
Median OS, mo26.923.5
(12.0-NE)(18.1-NE)
12-mo OS rate, %61.5%66.4%
(49.0-74.0)(58.1-74.6)
Median PFS, mo7.37.3
(4.9-12.0)(5.7-9.7)
12-mo PFS rate, %36.5%32.5%
(24.0-48.9)(24.2-40.8)
rn

NE, not estimable.

rna

TC ≥ 50% or IC ≥ 10% PD-L1–expressing cells.

rnb

TC or IC ≥ 5% PD-L1–expressing cells.

rn

Clinical trial identification

NCT02031458

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding

F. Hoffmann-La Roche Ltd/Genentech Inc, a member of the Roche Group

Disclosure

M.C. Garassino: Honoraria, Consulting, Speaker\'s Bureau, research funding, expert testimony, travel expenses: MSD, BMS, AZ, Lilly, Roche. D. Christoph: Honoraria, Speaker\'s Bureau: BI, BMS, Chugai, Novartis, Merck, MSD, Pfizer, Roche; Consulting: BI, BMS, Novartis, Pfizer, Roche; Expert testimony: BI, BMS, Novartis, Pfizer, Roche. J. Chaft: Advisor for Genentech and Astra Zeneca. M.L. Johnson: Consulting: Genentech, Celgene, BI; Research funding: OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati, Genmab, Pfizer, AZ, Roche/Genentech, Stemcentrix, Novartis, Checkpoint, Array, Regeneron. S. Mocci: Employee, stock: Roche/Genentech. S.N. Gettinger: Consulting: BMS; Research funding: Roche/Genentech, BMS, ARIAD, Incyte, Celldex. E. Felip: Advisory Boards: Lilly, Pfizer, BI, MSD, Roche; Speaker\'s Bureau: AZ, BMS, Novartis. All other authors have declared no conflicts of interest.