3P - Exploratory efficacy analysis by smoking status in PD-L1 high patients in the phase III, non-small cell lung cancer (NSCLC) IMpower110 study

Background

Metastatic NSCLC is a leading cause of cancer death globally. Although implementation of immunotherapies has improved overall survival (OS), certain subgroups such as never smokers appear to derive less benefit from immunotherapy monotherapy. This analysis of the IMpower110 trial explores the efficacy of atezolizumab compared to chemotherapy in the PD-L1 high (TC≥50%/IC≥10%) patients by smoking status, as well as the achievement of long-term benefit (LTB) in the ever-smoking population.

Methods

We analyzed baseline characteristics and efficacy outcomes (OS and progression-free survival (PFS)) in the aforementioned population and clinically relevant subgroups. Kaplan-Meier curves and forest plots are presented. We characterized the LTB population, defined as patients who lived ≥2 years since randomization. We performed Chi-square tests to assess factors associated with LTB.

Results

In the PD-L1 high population the OS HR was 1.80 (0.71-4.52) for never smokers and 0.71 (0.49-1.04) for ever-smokers. The following results refer to the ever-smoking, PD-L1 high population, which consists of 181 patients (88.3% of all patients with high PD-L1 expression by SP142): The median follow-up was 30.6 months (mo). A median OS of 23.13 mo in the atezolizumab arm was observed compared to 11.04 mo with chemotherapy (HR= 0.71; 95% CI: 0.49-1.04; p=0.079). Likewise, median PFS favored atezolizumab with 8.34 vs 4.88 mo (HR= 0.56; 95% CI: 0.40-0.78; p<0.001). LTB was achieved by 46% (n=45) of patients who received atezolizumab and 33% (n=27) of patients who received chemotherapy. In the atezolizumab arm, clinical factors such as ECOG, liver metastases and race were significantly associated with LTB.

Conclusions

This exploratory analysis of the IMpower110 study reiterates the difference in the efficacy of monotherapy immunotherapy compared to chemotherapy based on smoking status. Atezolizumab is associated with better efficacy outcomes and provided LTB in a higher number of patients compared to chemotherapy in the ever-smoking PD-L1 high population.

Legal entity responsible for the study

Roche Pharma.

Funding

Roche Pharma.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar, Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, President: ASEICA (Spanish Association of Cancer Research); Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. M.R. García-Campelo: Financial Interests, Personal, Speaker, Consultant, Advisor, travel/accomodation/expenses: Roche, Merck, BMS, AstraZeneca, Lilly, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: PharmaMar, Bayer, AbbVie, GSK, Boehringer. M.D. Isla Casado: Financial Interests, Personal, Speaker, Consultant, Advisor, travel/accomodation/expenses: Roche, Merck, BMS, AstraZeneca, Lilly, Pfizer, Amgen, Boehringer; Financial Interests, Personal, Research Grant: BMS, Roche, AstraZeneca, Lilly; Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer; Financial Interests, Personal, Advisory Role: AbbVie, Takeda. E. Carcereny: Financial Interests, Personal, Advisory Role, travel/accomodation/expenses: Roche, Bristol Myers Squibb, MSD, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer, Novartis; Financial Interests, Personal, Other, travel/accomodation/expenses: Pfizer. D. Rodriguez Abreu: Financial Interests, Personal, Speaker, Consultant, Advisor, travel/accomodation/expenses: Roche, Merck, BMS, AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer, Takeda. J.J. Garcia Gonzalez: Financial Interests, Personal, Speaker, Consultant, Advisor, travel/accomodation/expenses: Roche; Financial Interests, Personal, Advisory Role, travel/accomodation/expenses: Merck, BMS, Boehringer; Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Pfizer. D. Perez Parente: N. Gonzalez Mancha, E. Vilas,P. Ruiz Gracia, A. Greco: Financial Interests, Institutional, Member, employee: Roche Pharma Spain. D.R. Spigel: Consulting or Advisory Role: Genentech/Roche (Inst), Novartis (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), GSK (Inst), Amgen (Inst), Ipsen (Inst), Jazz Pharmaceuticals (Inst), Sanofi/Aventis (Inst), Novocure (Inst), Regeneron (Inst), Lilly (Inst), AbbVie (Inst), BeiGene (Inst), Lyell (Inst), Monte Rosa Therapeutics (Inst). Research Funding: Genentech/Roche (Inst), Novartis (Inst), Celgene (Inst), Bristol Myers Squibb (Inst), Lilly (Inst), AstraZeneca (Inst), University of Texas Southwestern Medical Center-Simmons Cancer Center (Inst), Merck (Inst), G1 Therapeutics (Inst), Neon Therapeutics (Inst), Takeda (Inst), Nektar (Inst), Celldex (Inst), Clovis Oncology (Inst), Daiichi Sankyo (Inst), EMD Serono (Inst), Astellas Pharma (Inst), GRAIL (Inst), Transgene (Inst), Aeglea Biotherapeutics (Inst), Ipsen (Inst), BIND Therapeutics (Inst), Eisai (Inst), ImClone Systems (Inst), Immunogen (Inst), Janssen Oncology (Inst), MedImmune (Inst), Molecular Partners (Inst), Agios (Inst), GSK (Inst), Tesaro (Inst), Cyteir (Inst), Apollomics (Inst), Novocure (Inst), Elevation Oncology (Inst), Calithera Biosciences (Inst), Arcus Biosciences (Inst), Arrys Therapeutics (Inst), Bayer (Inst), BeiGene (Inst), BioNTech (Inst), Blueprint Medicines (Inst), Boehringer Ingelheim (Inst), Hutchison MediPharma (Inst), Incyte (Inst), Kronos Bio (Inst), Loxo Oncology (Inst), Macrogenics (Inst), Oncologie (Inst), Pfizer (Inst), PTC Therapeutics (Inst), PureTech (Inst), Razor Genomics (Inst), Repare Therapeutics (Inst), Rgenix (Inst), Tizona Therapeutics Inc (Inst), Verastem (Inst), AbbVie (Inst), Amgen (Inst), AnHeart Therapeutics (Inst), Ascendis Pharma (Inst), Asher Biotherapeutics (Inst), Ellipses Pharma (Inst), Endeavor (Inst), Erasca (Inst), Evelo Biosciences (Inst), Faeth Therapeutics (Inst), Foundation Bio (Inst), FujiFilm Pharmaceuticals (Inst), Gilead Sciences (Inst), Janux Therapeutics (Inst), Jazz Pharmaceuticals (Inst), Lyell Immunopharma (Inst), Millennium Pharmaceuticals (Inst), Moderna (Inst), Monte Rosa Therapeutics (Inst), Peloton Therapeutics (Inst), SeaGen (Inst), Shenzhen Chipscreen Biosciences (Inst), Strata Oncology (Inst), Stemline Therapeutics (Inst), Synthekine (Inst), Taiho (Inst), Tango Therapeutics (Inst), Tarveda (Inst), and Zai Laboratory (Inst). F. de Marinis: Consulting or Advisory Role: AstraZeneca, MSD Oncology, Bristol Myers Squibb, Roche/Genentech, Pfizer, Novartis, Takeda. J. Jassem: Consulting or Advisory Role: AstraZeneca, Amgen, Boehringer Ingelheim.