Combined VEGF/PD-L1 Inhibition Displays Frontline Efficacy in ES-SCLC

According to the primary objective analysis, 77.4% of patients had died after a median follow-up time of 23.4 months, including 36 due to disease progression, 4 due to toxicity, and 1 due to massive blood loss.

The combination of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and etoposide elicited frontline efficacy in patients with extensive-stage small cell lung cancer (ES-SCLC), meeting the primary end point of 1-year overall survival (OS) in the single-arm phase 2 GOIRC-01-2019 CeLEBrATE study (NCT04730999), the findings of which were published in the Journal for ImmunoTherapy of Cancer.1

According to the primary objective analysis, 77.4% (n = 41/53) of patients had died after a median follow-up time of 23.4 months (95% CI, 21.1-26.0), including 36 due to disease progression, 4 due to toxicity, and 1 due to massive blood loss. Additionally, the 1-year OS rate in those who received study treatment was 61.8% (90% CI, 50.7%-72.8%; P = .04), with a median OS of 12.9 months (95% CI, 11.6-17.5).

Additional efficacy data showed that among response-evaluable patients (n = 48), the objective response rate (ORR) was 83.3% (95% CI, 69.8%-92.5%), with 40 patients attaining a partial response, 4 attaining stable disease, and 4 experiencing progressive disease as the best response. The median duration of response was 4.2 months (95% CI, 4.0-5.8). Additionally, a median progression-free survival (PFS) of 6.2 months (95% CI, 5.4-6.6) was observed after 43 patients experienced progressive disease, and 7 had died without radiological evidence of disease progression.

“The combination of bevacizumab, atezolizumab, carboplatin, and etoposide is feasible and active in the first-line treatment of patients with ES-SCLC,” lead investigator Giuseppe Lamberti, MD, PhD, assistant professor of the Department of Experimental, Diagnostic and Specialty Medicine Dimes at the University of Bologna, wrote in the publication with study coinvestigators. “Though toxicity must be carefully managed through adequate patient selection and proper use of G-CSF prophylaxis, data from the [phase 2] CeLEBraTE study suggest that the combined inhibition of angiogenesis and immune checkpoints may be effective in a challenging disease setting such as ES-SCLC.”

Those enrolled in the phase 2 study received an induction phase of treatment consisting of carboplatin at an area under the curve of 5 ml/min on day 1, 100 mg/m2 of etoposide on days 1 to 3, 7.5 mg/kg of bevacizumab on day 1, and 1200 mg of atezolizumab on day 1 of 21-day cycles for 4 to 6 cycles. Additionally, patients received 7.5 mg/kg of bevacizumab and 1200 mg of atezolizumab on day 1 of 21-day cycles for a maximum of 18 cycles as maintenance therapy.

Among patients treated with the investigational regimen (n = 53), 54.7% were male, the median age was 65 years (range, 46-79), and 49.1% were former smokers. A total of 58.5% of patients had an ECOG performance score of 0; 18.9%, 24.5%, and 22.6% had brain, liver, and bone metastases, respectively; and the median sum of the diameter of target lesions was 118 mm (range, 17-240). The median number of induction cycles completed was 4 (range, 1-6), with 58.5% completing 4 cycles, and an additional 28.3% completing more than 4.

Among this patient group, 86.8% started maintenance therapy, with a median of 5.5 cycles (range, 1-37) completed for those who were treated. The median number of total treatment cycles completed was 9 (range, 1-41). A total of 32.1% of patients received treatment beyond progressive disease for a median of 2 cycles (range, 1-10).

The primary end point was 1-year OS rate. Secondary end points included ORR, PFS, and safety.

Among patients who were treated (n = 53), 49 discontinued study treatment: 38 due to progressive disease, 5 due to death without radiological progression, 2 due to patient refusal, and 4 due to other reasons. Grade 3 to 4 adverse effects (AEs) occurred in 64.2% of patients, including 56.6% of patients who experienced grade 3 or 4 hematologic AEs. The most common grade 3 or 4 hematological AEs included neutropenia (52.8%), anemia (7.6%), leukopenia, thrombocytopenia, and febrile neutropenia (5.7% each).

Dose reductions related to toxicity-associated events occurred in 45.3% of patients during the induction phase, and dose delays occurred in 73.6% of patients in the induction phase and 69.6% in the maintenance phase. No treatment discontinuations occurred due to toxicity. Serious AEs occurred in 58.5% of patients, of which 35.8% were related to treatment. A total of 4 grade 5 AEs occurred, including 2 septic shocks during febrile neutropenia and single instances of pancytopenia and pancreatitis.

Reference

Lamberti G, Rihawi K, Mazzoni F, et al. Carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of patients with extensive stage small-cell lung cancer: the GOIRC-01-2019 CeLEBrATE study. J Immunother Cancer. 2025;13:e010694. doi:10.1136/jitc-2024-010694