379MO - 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: 379MO

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 6 February, 2017.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was 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: Research grant/Funding (institution): Genentech; AstraZeneca; Advisory/Consultancy, Advisory board: Genentech; AstraZeneca. M.C. Garassino: Research grant/Funding (institution), Grants and personal fees: Eli Lilly, Otsuka Pharmaceutical, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Incyte, Bayer, MSD, GlaxoSmithKline, Spectrum Pharmaceuticals, Blueprint Medicines; Research grant/Funding (self), Personal fees: Boehringer Ingelheim, Inivata, Takeda, Sanofi, Seattle Genetics, Daiichi-Sankyo, Janssen; Research grant/Funding (institution), Grants: Tiziana Life Sciences, Clovis, Merck Serono, United Therapeutics Corporation, Merck KGaA, Turning Point Therapeutics, Ipsen, Exelisis; Non-remunerated activity/ies, Non-financial support: MSD, Pfizer, Eli Lilly. Y. Chen: Research grant/Funding (institution): AstraZeneca / spen / Roche, BMS; Advisory/Consultancy, Personal fees (consultancy): Pfizer, Array Biopharma, AstraZeneca, Genentech, BMS, Novartis, Takeda; Speaker Bureau/Expert testimony, Personal fees (speaker bureau): AstraZeneca, Genentech, BMS, Merck, Novartis, Takeda, Eli Lilly, Guardant Health. N. Reinmuth: Research grant/Funding (self), Personal fees: AstraZeneca, Boehringer Ingelheim Hoffmann La-Roche, MSD Sharp & Dohme, Takeda, BMS, Pfizer; Non-remunerated activity/ies, Non-financial support: AstraZeneca, Boehringer Ingelheim, Hoffmann La-Roche, AbbVie, BMS, Pfizer. K. Hotta: Research grant/Funding (self), Research grant/Funding (institution), Research grant and personal fees: AstraZeneca, Lilly, BMS, MSD, Chugai; Research grant/Funding (self), Personal fees: Pfizer, Ono, Nippon Kayaku, Taiho, Boehringer Ingelheim, Novartis, Daiichi-Sankyo, Kyorin; Research grant/Funding (institution), Research grant: Astellas. M. Özgüroğlu: Advisory/Consultancy: Janssen, Sanofi, Astellas; Honoraria (self): Novartis, Roche, Janssen, Sanofi, Astellas; Honoraria (institution): Novartis, Roche, Janssen, Sanofi, Astellas; Travel/Accommodation/Expenses: BMS, Janssen. S. Spencer, M. Xie, S. Jones, A. Franks, Y. Shrestha: Full/Part-time employment: AstraZeneca. L. Paz-Ares: Honoraria (self), Travel/Accommodation/Expenses, Spouse/Financial dependant: Merck Sharp and Dohme; Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Spouse/Financial dependant: Roche/Genentech; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Spouse/Financial dependant: Novartis; Honoraria (self), Spouse/Financial dependant: Amgen; Honoraria (self): Incyte; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Blueprint Medicines; Honoraria (self): Bayer; Leadership role: Altum Sequencing; Leadership role: Genomica; Honoraria (self): PharmaMar; Honoraria (self), Spouse/Financial dependant: Ipsen; Travel/Accommodation/Expenses: AstraZeneca Spain; Honoraria (self): Celgene; Honoraria (self): Sysmex; Spouse/Financial dependant: Servier; Spouse/Financial dependant: Sanofi. All other authors have declared no conflicts of interest.