LBA61 - Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase III CASPIAN study

Background

In CASPIAN, the Phase 3 study of etoposide + cisplatin/carboplatin (EP) ± durvalumab (D) ± tremelimumab (T) as first-line treatment of ES-SCLC, D + EP demonstrated a statistically significant improvement in OS vs EP alone (data cut-off [DCO]: 11 Mar 2019; HR 0.73 [95% CI 0.59–0.91; p=0.0047]). In a subsequent analysis after a median follow-up of 25.1 mo (DCO 27 Jan 2020), OS benefit with D + EP vs EP was sustained (HR 0.75 [95% CI 0.62–0.91; nominal p=0.0032]), and D + T + EP numerically improved OS vs EP (HR 0.82 [95% CI 0.68–1.00; p=0.0451]), but did not reach statistical significance (p≤0.0418). Here we report updated OS after a median follow-up of >3 years, the longest reported to date for a phase 3 trial of EP + PD(L)1 in this disease setting.

Methods

Pts with treatment-naïve ES-SCLC were randomised 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. Pts in the IO arms received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w. Pts in the EP arm received up to 6 cycles of EP. The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Serious AEs (SAEs) were assessed during long-term follow up.

Results

268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively. At a DCO of 27 Mar 2021, median follow-up was 39.4 mo, 86% maturity. D + EP continued to demonstrate improved OS vs EP: HR 0.71 (95% CI 0.60–0.86; nominal p=0.0003). Median OS was 12.9 vs 10.5 mo; 22.9% vs 13.9% of pts were alive at 24 mo; and 17.6% vs 5.8% of pts were alive at 36 mo with D + EP vs EP, respectively. D + T + EP continued to numerically improve OS vs EP: HR 0.81 (95% CI 0.67–0.97; nominal p=0.02); median OS was 10.4 mo, and 15.3% of pts were alive at 36 mo. 46 pts remained on treatment with D at DCO (27 in the D + EP arm and 19 in the D + T + EP arm). In D + EP, D + T + EP and EP arms, respectively, incidences of SAEs (all cause) were 32.5%, 47.4% and 36.5%; and AEs leading to death (all cause) were 5.3%, 10.9% and 6.0%.

Conclusions

D + EP demonstrated sustained OS benefit over EP with a well-tolerated safety profile after >3 years of median follow-up, consistent with previous analyses. 3 times more pts were estimated to be alive at 3 years when treated with D + EP vs EP alone, further establishing D + EP as standard of care for first-line treatment of ES-SCLC.

Clinical trial identification

NCT03043872 (release date: February 6, 2017).

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Ashfield Health company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Leadership Role: Genomica, Altum Sequencing; Financial Interests, Personal, Other, Personal fees [travel, accommodation, other expenses]: Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol Myers Squibb, Lilly, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Genentech, Lilly, Pfizer, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Sysmex, Bayer, Amgen, Blueprint Medicines, Incyte; Financial Interests, Personal, Other, Fees (immediate family member): Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, Merck. Y. Chen: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Writing Engagements: AstraZeneca, IPSEN; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, IPSEN, EMD Serono; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck, Guardant Health, Pfizer, Jazz Pharmaceuticals, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck, IPSEN, Jazz Pharmaceuticals. N. Reinmuth: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, MSD, Merck, Pfizer, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, MSD, Merck, Pfizer, Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Amgen, AstraZeneca, Beigene, BMS, Daiichi Sankyo, IO Biotech, Janssen-cilag International NV, Jiangsu Hengrui Medicine, Lilly, Merck, Merck Sharp & Dohme Corp, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Takeda. K. Hotta: Financial Interests, Personal, Speaker’s Bureau: Pfizer, AstraZeneca, Chugai, Lilly, Takeda, MSD, BMS, Ono, NipponKayaku, Taiho, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, Chugai, Lilly, BMS. M.J. Hochmair: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly. J.H. Ji: Non-Financial Interests, Personal, Invited Speaker: LG life Sciences; Non-Financial Interests, Personal, Advisory Board: HK inno.N; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Roche, Hyndai Pharm, Celltrion, Boryung Pharm. I. Bondarenko: Financial Interests, Personal and Institutional, Principal Investigator: Amgen, AstraZeneca, BMS, Lilly, Merck Sharp & Dohme Corp, Novartis, Pfizer, Roche, Sanofi, Takeda, Tesaro. H.L. Broadhurst: Financial Interests, Personal, Full or part-time Employment, Contracted to AastraZeneca: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T. Dalvi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Jiang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Genentech, Janssen, Pfizer; Non-Financial Interests, Personal and Institutional, Research Grant: AbbVie, Advaxis, Array/Pfizer, AstraZeneca, BMS, Eli Lilly, Genentech, Merck, Pfizer, Puma, Spectrum, Tesaro, Vaccinex; Non-Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, Advaxis, Array/Pfizer, AstraZeneca, BMS, Eli Lilly, Genentech, Merck, Pfizer, Puma, Spectrum, Tesaro, Vaccinex. All other authors have declared no conflicts of interest.