LBA86 - Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L ES-SCLC: Characterization of long-term clinical benefit and tumour mutational burden (TMB) in CASPIAN

Background

In the phase III CASPIAN trial, 1L D+EP significantly improved OS vs EP (HR 0.73 [95% CI 0.59‒0.91; p=0.0047]) in pts with ES-SCLC, with sustained benefit after >2 yr median follow-up (HR 0.75 [95% CI 0.62‒0.91; nominal p=0.0032]). Landmark analyses indicated 22% of pts were alive at 24m with the addition of D±T to EP. Here we assess the clinical characteristics and outcomes of pts deriving long-term benefit, as well as the relationship between TMB and efficacy outcomes in the ITT population.

Methods

805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP, or EP. Exploratory subgroup analyses defined long-term clinical benefit as PFS ≥12m. Tumour tissue was mandated at screening, if available. TMB was assessed in tissue (tTMB) using the FoundationOne CDx platform.

Results

45 (17%), 42 (16%), and 12 (5%) pts treated with D+EP, D+T+EP, and EP had PFS ≥12m, respectively (data cutoff 27 Jan 2020). In all arms, the PFS ≥12m subgroup had a higher incidence of favorable prognostic factors (more women and pts with PS 0, fewer pts with brain/liver metastases). In the D+EP arm, pts with PFS ≥12m received more D (median 25 vs 7 cycles) and had improved ORR (96% vs 63%), median DoR (NR vs 4m) and OS at 24m (77% vs 11%) compared with the PFS <12m subgroup (Table). Similar results were observed with EP and when both IO arms were combined. Safety and additional efficacy outcomes in the subgroups will be presented. Across all 3 arms, 283 pts (35% of ITT) were evaluable for tTMB. tTMB was not predictive of a differential treatment effect for D±T+EP vs EP (OS, PFS, or ORR). Table: LBA86

Conclusions

Across all arms, pts with PFS ≥12m had exceptional 2 yr OS rates >75%, despite some having poor prognostic factors such as baseline brain or liver metastases. There were >3 times more pts deriving long-term benefit when treated with durvalumab + EP vs EP alone. Further investigation into predictive factors for long-term benefit with durvalumab is ongoing.

Clinical trial identification

NCT03043872; release date: February 6, 2017.

Editorial acknowledgement

Medical writing provided by Beena John, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

J.W. Goldman: Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Research grant/Funding (institution): Tiziana Life Sciences; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): United Therapeutics Corporation; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy: Janssen; Non-remunerated activity/ies: Turning Point; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Exelixis. Y. Chen: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Eli-Lilly; Speaker Bureau/Expert testimony: Guardant Health; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Array Biopharma; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Roche. N. Reinmuth: Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Boehringer Ingelheim; Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Hoffman la-Roche; Honoraria (self): MSD Sherp & Dohme Gmbh; Honoraria (self): Takeda; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Pfizer. K. Hotta: Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli-Lilly; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): Ono; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Nippon Kayaku; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Novartis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Kyorin; Research grant/Funding (institution): Astellas. M. Özgüroğlu: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self): Novartis; Honoraria (self): Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb. S. Spencer: Full/Part-time employment: AstraZeneca. M. Xie: Full/Part-time employment: AstraZeneca. S. Jones: Full/Part-time employment: AstraZeneca. A. Franks: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. Y. Shrestha: Full/Part-time employment: AstraZeneca. L. Paz-Ares: Leadership role, Myself: Genomica, Altum Sequencing; Travel/Accommodation/Expenses: Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Lilly, Pfizer; Honoraria (self): Roche/Genentech, Lilly, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme; Honoraria (self): AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Sysmex, Bayer, Amgen, Blueprint, Incyte; Spouse/Financial dependant, Fees [immediate family member]: Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, Merck. All other authors have declared no conflicts of interest.