141O - Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L extensive-stage (ES) SCLC: characteristics of long-term survivors in the CASPIAN study

Background

In the phase 3 CASPIAN trial, 1L D+EP significantly improved OS vs EP and OS benefit was sustained after >3 years median follow-up (HR 0.71; 95% CI 0.60‒0.86; nominal p=0.0003). Here we assess clinical and molecular characteristics of pts who experienced long-term survival in CASPIAN.

Methods

805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP or EP. In post-hoc analyses, clinical characteristics were assessed in long-term survivors (LTS; n=94), defined as pts still alive at the 22 Mar 2021 data cutoff (DCO; median follow-up 39.4 mo). PD-L1 expression and tissue tumour mutational burden (tTMB) were assessed in the biomarker evaluable populations (BEPs) according to OS landmark (18 and 36 mo).

Results

There were 44 (16%), 37 (14%) and 13 (5%) LTS in the D+EP, D+T+EP and EP arms, respectively. LTS had slightly higher incidence of some favourable prognostic factors at baseline; incidence of brain/liver mets was lower among LTS vs ITT, although they still occurred in some LTS (Table). More LTS received ≥4 cycles EP than ITT, with a higher median overall treatment exposure in the IO+EP arms. 46 (27 D+EP; 19 D+T+EP) LTS were ongoing D treatment at this DCO. ORR and 24-mo PFS rates were higher for LTS vs ITT in the IO+EP arms. Rates of serious AEs (SAEs) were similar in LTS and ITT (Table). In the D+T+EP arm only, incidence of PD-L1 expression on ≥1% of tumour cells (TC) or immune cells (IC) (but not tTMB >10 mut/Mb) was enriched in pts with OS ≥18 mo vs OS <18 mo (Table); enrichment was maintained with OS ≥36 mo (data will be presented).

Conclusions

There were >3 times as many LTS in the D+EP arm vs the EP arm. LTS were more likely to have favourable prognostic characteristics than ITT, although some LTS had brain/liver mets at baseline. Notably, most LTS completed EP induction and, in both the IO+EP arms, had substantially greater overall treatment exposure, as well as achieving higher ORR and longer PFS, vs ITT. There was no evidence of cumulative toxicity based on SAEs.Table: 141O

*Based on etoposide^†From 27 Jan 2020 DCO; RECIST data not collected after this DCO

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

N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Hoffmann-La Roche; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Advaxis; Non-Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Genentech; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Advaxis; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Pfizer. M.C. Garassino: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD International GmbH; Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Boehringer Ingelheim Italia S.p.A; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: Ignyta; Financial Interests, Personal, Other: Genetics; Financial Interests, Personal, Other: Mirati; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Regerenon; Financial Interests, Institutional, Other: Eli Lilly; Financial Interests, Institutional, Other: MSD; Financial Interests, Institutional, Other: Pfizer (MISP); Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: MSD International GmbH; Financial Interests, Institutional, Other: Bristol Myers Squibb; Financial Interests, Institutional, Other: Boehringer Ingelheim Italia S.p.A; Financial Interests, Institutional, Other: Celgene; Financial Interests, Institutional, Other: Eli Lilly; Financial Interests, Institutional, Other: Ignyta; Financial Interests, Institutional, Other: Incyte; Financial Interests, Institutional, Other: MedImmune; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Takeda; Financial Interests, Institutional, Other: Tiziana; Financial Interests, Institutional, Other: Foundation Medicine; Financial Interests, Institutional, Other: Glaxo Smith Kline GSK; Financial Interests, Institutional, Other: Spectrum pharmaceuticals ; Financial Interests, Institutional, Research Grant: AIRC; Financial Interests, Institutional, Research Grant: AIFA; Financial Interests, Institutional, Research Grant: Italian Moh; Financial Interests, Institutional, Research Grant: TRANSCAN. Y. Chen: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Guardant Health; Financial Interests, Personal, Other, Honoraria: Jazz Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Research contract and support for meeting attendance/travel: Ipsen. K. Hotta: Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Ono; Financial Interests, Personal, Speaker’s Bureau: Taiho; Financial Interests, Personal, Speaker’s Bureau: Boehringer-Ingelheim; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Chugai; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: AbbVie. M.J. Hochmair: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda. G. Statsenko: Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: MCD; Financial Interests, Personal, Principal Investigator: AbbVie; Financial Interests, Personal, Principal Investigator: BeiGene. H. Mann: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Xie: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Y. Shrestha: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P. Chugh: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. T. Dalvi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. L. Paz-Ares: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Jannsen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Mirati; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: PharmaMar; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Member of the Board of Directors: Genomica; Financial Interests, Personal, Member of the Board of Directors: Altum sequency; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. All other authors have declared no conflicts of interest.