LBA2 - First-line (1L) durvalumab plus platinum-etoposide for patients with extensive-stage SCLC (ES-SCLC): Primary results from the Phase 3b LUMINANCE study

Background

The phase 3 CASPIAN study (NCT03043872) of 1L D + EP (4 cycles) vs EP alone (up to 6 cycles) in pts with ES-SCLC (WHO performance status [PS] 0–1) established D + EP as a global standard of care. However, like most phase 3 registration studies, elements of the study design did not fully reflect real-world clinical practice. The phase 3b LUMINANCE study (NCT04774380) evaluated D + up to 6 cycles of EP in pts with ES-SCLC, including those with WHO PS 2. We report results of the primary analysis.

Methods

Pts with treatment (tx)-naïve ES-SCLC and WHO PS 0–2 received D 1500 mg + EP Q3W for up to 6 cycles (investigator decision), followed by D Q4W until progression. Primary endpoints were rates of grade ≥3 AEs and immune-mediated AEs (imAEs); secondary endpoints included objective response rate (ORR), duration of response (DoR), PFS and OS.

Results

As of 12 June 2023, 152 pts from 32 sites/5 countries had received tx, median follow-up was 37.3 weeks and 23.7% were still receiving D. Median age was 64.0 years, 64.5% of pts were male and 99.3% were white. Median no. of D doses was 8.5 (Table); 63.8% of pts received carboplatin and 38.8% received cisplatin. Grade ≥3 AEs occurred in 59.2% of pts (Table); most common were neutropenia (26.3%), anaemia (9.9%) and neutrophil count decreased (7.9%). Grade ≥3 AEs occurred in 44/66 (66.7%) and 45/85 (52.9%) pts who received 1–4 or ≥5 cycles of EP*, respectively. imAEs occurred in 13.8% of pts; most common was hypothyroidism (6.6%). Confirmed ORR (95% CI) was 65.8% (57.7–73.3); median PFS (95% CI) was 6.2 (5.3–6.5) months (mo); and median OS (95% CI) was 13.1 (10.1–not estimable [NE]) mo. Numerically better outcomes were observed in pts who received ≥5 cycles of EP (Table). Table: LBA2

*Based on etoposide; 1 pt received no etoposide. ^†4 possibly related to EP; none to D. ^‡Based on platinum. NR, not reached

Conclusions

Safety and efficacy findings from LUMINANCE, including those pts who received ≥5 cycles of induction chemo-IO, were consistent with those observed in CASPIAN. The results further support the use of D + EP as 1L tx for pts with ES-SCLC.

Clinical trial identification

NCT04774380; March 1, 2021.

Editorial acknowledgement

Medical writing support for this abstract, under the direction of the authors, was provided by Clair Clowes of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GSK, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, Janssen, MSD, Merck, Pfizer, Symphogen and Takeda. N.B. Leighl: Financial Interests, Personal, Other, Travel funding for CME meetings: AstraZeneca. D. Galetta: Non-Financial Interests, Personal, Speaker’s Bureau: Roche, Eli Lilly, MSD, BMS, Novartis, Takeda, Janssen; Financial Interests, Personal, Advisory Board: BMS, Novartis. M.A.N. Sendur: Financial Interests, Personal, Speaker’s Bureau: Roche, Astra Zeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda. E. Bria: Financial Interests, Personal, Invited Speaker: Merck-Sharp & Dome, AstraZeneca, Pfizer, Eli Lilly, Bristol Myers Squibb, Novartis, Takeda and Roche; Financial Interests, Personal, Advisory Board: Merck-Sharp & Dome, AstraZeneca, Pfizer, Eli Lilly, Bristol Myers Squibb, Novartis and Roche; Non-Financial Interests, Institutional, Research Grant: AstraZeneca and Roche; Non-Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dome, AstraZeneca, Pfizer, Eli Lilly, Janssen and Roche; Financial Interests, Personal, Member: ASCO, IASLC, ESMO, AIOM; Non-Financial Interests, Personal, Advisory Role: Comitato Tecnico Scientifico, AIRC (Italian Association for Cancer Research). I. Cicin: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Pfizer, Servier, Merck Sharp & Dohme, Eli Lilly, Bristol Myers Squibb, AstraZeneca, Merck, Astellas, AbbVie, Nobel, and Abdi Ibrahim Gen; Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Servier, Merck Sharp & Dohme, Eli Lilly, Bristol Myers Squibb, AstraZeneca, Merck, Astellas, AbbVie, Nobel, and Abdi Ibrahim, Gen; Financial Interests, Personal, Principal Investigator: Takeda, Gilead, Roche, Novartis, Pfizer, Tahio, Servier, Merck Sharp & Dohme, Yuhan, Eli Lilly, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca, BeiGene, Merck, Astellas, Sanofi, GSK, Bayer, and AbbVie; Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Servier, Merck Sharp & Dohme, Eli Lilly, Bristol Myers Squibb, AstraZeneca, Merck, Astellas, AbbVie, Nobel, and Abdi Ibrahim Gen. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Takeda, Pfizer, Sanofi, Janssen, Eli Lilly, Thermo Fisher, Roche, Novartis; Financial Interests, Personal, Speaker’s Bureau: AZ, MSD, Takeda, Pfizer, Sanofi, Janssen, Eli Lilly, Thermo Fisher, Roche, Novartis; Financial Interests, Personal, Advisory Board: AZ, MSD, Takeda, Pfizer, Sanofi, Janssen, Eli Lilly, Roche, Novartis. M. Hodari: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Donner: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. F. de Marinis: Financial Interests, Personal, Advisory Board: AZ, MSD, Roche, Pfizer, Janssen, Merck, BMS. All other authors have declared no conflicts of interest.