Anti-Angiogenesis Plus ICIs, Chemo Improve Frontline Efficacy in ES-SCLC

A subgroup analysis carried out across 5 dimensions, including gender, age, performance status, brain metastasis status, and liver metastasis status, revealed an OS imbalance for patients younger than 65 years old with an HR of 0.42.

Angiogenesis inhibition, when added to frontline immunochemotherapy, improved efficacy outcomes, including progression-free survival (PFS) and objective response rate (ORR), in patients with untreated extensive-stage small cell lung cancer (ES-SCLC), according to a comprehensive analysis of 10 phase 3 randomized, controlled trials (INPLASY2023110061) published in Therapeutic Advances in Medical Oncology.1

Efficacy data revealed that the addition of angiogenesis inhibitors to immunochemotherapy did not significantly improve overall survival (OS) vs immunochemotherapy alone (HR, 0.97; 95% CI, 0.79-1.19). Moreover, no significant differences in OS were observed across anti-angiogenesis regimens in ES-SCLC. Benmelstobart (Andevil) with anlotinib plus chemotherapy had the highest probability of enhancing OS at 41% according to Bayesian ranking profiles.

A PFS analysis found that patients treated with angiogenesis inhibitors had enhanced PFS outcomes vs those who were not (HR, 0.56; 95% CI, 0.47-0.66). Furthermore, the benmelstobert regimen surpassed all alternative treatments, achieving the highest probability of improving PFS per Bayesian ranking profiles at 98%. Furthermore, atezolizumab (Tecentriq)-bevacizumab (Avastin)-chemotherapy exhibited increased PFS relative to atezolizumab-chemotherapy (HR, 0.67; 95% CI, 0.52-0.86), pembrolizumab (Keytruda)-chemotherapy (HR, 0.64; 95% CI, 0.44-0.95), and durvalumab (Imfinzi)-chemotherapy (HR, 0.64; 95% CI, 0.44-0.95).

Additionally, an ORR analysis revealed that the addition of angiogenesis inhibitors to immunochemotherapy significantly increased ORR, with an odds ratio (OR) of 1.64 (95% CI, 1.17-2.31), showing worse outcomes with immunochemotherapy alone. Additionally, the benmelstobert regimen significantly increased ORR vs atezolizumab-chemotherapy (OR, 2.59; 95% CI, 1.47-4.63), and no difference in ORR was seen between atezolizumab-bevacizumab-chemotherapy and all other anti-angiogenesis regimens. The benmelstobert regimen had the highest probability of achieving an ORR at 63%.

A subgroup analysis carried out across 5 dimensions, including gender, age, performance status, brain metastasis status, and liver metastasis status, revealed an OS imbalance for patients younger than 65 years old with (HR, 0.42; 95% CI, 0.29-0.61).

“To further enhance the therapeutic effect, angiogenesis inhibitors have been added to the first-line treatment. Currently, only a few studies directly compare the efficacy and toxicity of immunochemotherapy combined with angiogenesis inhibitors and immunochemotherapy,” Linjing Zhou, of the Department of Thoracic Medical Oncology at Zhejiang Cancer Hospital in China, wrote in the publication with study coinvestigators. “[T]his study indicated that immunochemotherapy combined with angiogenesis inhibitors has certain advantages in PFS and ORR in patients with untreated ES-SCLC. However, these benefits were not translated into improved OS, and only patients under 65 years old may potentially benefit from this co-treatment strategy.”

The study was populated by a systemic search of electronic medical databases initially performed February 3, 2024, and updated August 31, 2024. After initially identifying 632 studies from the database, 11 studies met the eligibility criteria for inclusion and included 4815 patients with untreated ES-SCLC.

Studies were selected if they were randomized controlled trials that included patients with histologically or cytologically confirmed ES-SCLC that assessed combinations of PD-1/PD-L1 inhibitors with or without angiogenesis inhibitors in the frontline setting. Studies were also included if they compared PD-1/PD-L1 combinations with or without angiogenesis inhibitors against other ES-SCLC approaches, and phase 2 or 3 trials were included that reported OS, PFS, and/or ORR outcomes, as well as adverse effects (AEs).

Safety findings from the comprehensive analysis revealed that the incidence of grade 3 or higher AEs was not significantly different between those treated with anti-angiogenesis vs those who were not (OR, 1.28; 95% CI, 0.81-2.04). Additionally, benmelstobart-anlotinib-chemotherapy was associated with a higher risk of grade 3 or higher AEs vs durvalumab-chemotherapy and tislelizumab-jsgr (Tevimbra)-chemotherapy (OR, 2.36; 95% CI, 1.01-5.60). Furthermore, nivolumab-chemotherapy had the highest probability of ranking first as being associated with the greatest risk of toxicity, at 50%.

Reference

Zhou L, Li Y, Wang K, et al. Efficacy and safety of first-line PD-1/PD-L1 inhibitors combined with or without anti-angiogenesis therapy for extensive-stage small-cell lung cancer: a network meta-analysis. Ther Adv Med Oncol. Published online June 25, 2025. doi:10.1177/17588359251348310