1994P - Carboplatin, etoposide, bevacizumab, and atezolizumab in patients with extensive-stage SCLC – GOIRC-01-2019 CeLEBrATE ML41241 trial

Background

PD-L1 inhibitors added to platinum etoposide improved survival in extensive stage small cell lung cancer (ES-SCLC). Bevacizumab added to platinum etoposide chemotherapy has been shown to be safe and active. VEGF has immunosuppressive effects in SCLC tumor microenvironment and combined PD-L1 and VEGF inhibition has synergistic antitumor effect in SCLC models.

Methods

This is an investigator-initiated phase II single arm trial sponsored by GOIRC with the unconditional financial support of Roche S.p.A. Patients received carboplatin (AUC 5), etoposide (100 mg/m²), bevacizumab (7.5 mg/kg), and atezolizumab (1200 mg) for 4-6 cycles (induction), followed by bevacizumab and atezolizumab (maintenance) every 3 weeks for up to 18 total cycles as first-line treatment for ES-SCLC. Asymptomatic or treated brain metastases and treatment with atezolizumab beyond RECIST-defined progression (PD) were allowed. The primary endpoint was 1-year OS.

Results

Enrollment completed in March 2022, so the primary endpoint is expected to be mature at the data cutoff of March 31st, 2023. Of 53 enrolled patients (45% women, median age 65 years), 22 (42%) had an ECOG PS of 1, 14 (26%) had liver, 11 (21%) bone, and 10 (19%) brain metastases. Median sum of target lesions diameters was 119.5 mm (range 17-240). Of 51 patients with available data, 40 (78%) completed induction and 37 (73%) started maintenance, with a median of 7 courses (range 1-18). Atezolizumab was administered beyond PD in 17 cases (33%), for a median of 2 courses (range 1-10), with 11 patients still on treatment at the data cut-off date. Adverse events are reported in table. Serious adverse events (SAE) were reported in 16 cases, including neutropenia (n=4), febrile neutropenia (n=3), and pulmonary embolism (n=3). Table: 1994P

Adverse events

Conclusions

The addition of bevacizumab to carboplatin-etoposide-atezolizumab in patients with ES-SCLC is overall well-tolerated. The survival analysis will be available and reported at the conference.

Clinical trial identification

Eudract 2019-003798-25.

Editorial acknowledgement

Legal entity responsible for the study

Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma, Italy.

Funding

GOIRC and Roche.

Disclosure

F. Mazzoni: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, MSD; Financial Interests, Personal, Invited Speaker: Takeda. C. Genova: Financial Interests, Personal, Invited Speaker, Speaker's Bureau (scientific meeting): AstraZeneca, BMS, Merck-Sharp-Dohme, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Board, Advisory board: AMGEN, Sanofi; Financial Interests, Personal, Advisory Board, Advisory Board: Roche, Takeda; Financial Interests, Institutional, Funding, Funding for support of translational study: BMS; Financial Interests, Institutional, Funding, Funding in support of translational study: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for translational study: Italian Ministry of Health; Non-Financial Interests, Principal Investigator, Local PI for clinical trials: AstraZeneca, Roche; Non-Financial Interests, Member, Scientific society membership: ASCO, AIOM, FONICAP, AIOT, IASLC, ISLB. G. Pasello: Financial Interests, Personal, Invited Speaker: Amgen, Lilly, Novartis, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, unconditioned support: AstraZeneca; Non-Financial Interests, Principal Investigator: AstraZeneca, Roche, Novartis, Lilly, Janssen, PharmaMar. M. Tiseo: Financial Interests, Personal, Financially compensated role: Roche, AstraZeneca, BMS, Pfizer, Novartis, MSD, Takeda, Otsuka, Pierre Fabre, Amgen, Merck, Sanofi. All other authors have declared no conflicts of interest.