Benmelstobart Ups ES-SCLC Survival

A four-drug combination, which includes two chemotherapies, significantly improves progression-free survival (PFS) and overall survival (OS) compared with chemotherapies alone in patients with newly diagnosed extensive-stage (ES) small cell lung cancer (SCLC). That's according to data from the randomized phase III ETER701 trial presented at the International Association for the Study of Lung Cancer's 2023 World Conference on Lung Cancer, held in Singapore, September 9–12.

“The results are striking, impressive, and really positive,” said study dis­cussant Noemi Reguart, MD, PhD, of the Hospital Clinic Barcelona in Spain.

SCLC is a recalcitrant malignancy. Immunochemotherapy had shown some promise, with a 2- to 4-month increase in OS, but “improving long-term survival remains an unmet need,” said Ying Cheng, MD, of the Jilin Cancer Hospital in Changchun, China, who presented the study's findings.

The complex microenvironment of SCLC, characterized by immuno­suppression, angiogenesis, and vascularization, hinders treatment effectiveness, explained Cheng. In an effort to reprogram the tumor microenvironment and increase immune cell infiltration, Cheng and her colleagues turned to a combination of Chia Tai Tianqing Pharmaceutical Group's PD-L1 inhibitor benmelstobart (TQB2450) and the angiogenesis inhibitor anlotinib (AL3818; FOCUS V; Advenchen Laboratories) with etoposide and carboplatin chemotherapy.

Researchers enrolled 738 patients from 72 cancer centers in China, with 246 patients assigned to receive benmelstobart, anlotinib, and chemotherapy and 247 to receive placebo plus chemotherapy; 245 patients were assigned to receive placebo plus anlotinib and the chemotherapy, but Cheng did not present data from this cohort.

After a median follow up of 14 months, those who received the four-drug combination had a median PFS of 6.9 months compared with 4.2 months in the placebo plus chemotherapy group, Cheng reported. The median OS was 19.3 months versus 11.9 months, respectively. The 6-month and 12-month PFS rates were 59.1% and 27.9% in the experimental arm and 16.6% and 2.3%, respectively, in the control arm.

Although 93.1% of patients who received benmelstobart experienced grade 3 or higher treatment-related adverse events (TRAE), 87% of patients who received only the chemotherapies did so. The most common of these TRAEs were decreases in neutrophils, platelets, and white blood cells. Overall, Cheng deemed the treatment manageable and tolerable.

These results are “extremely encouraging,” Cheng said, adding that the benmelstobart, anlotinib, and chemotherapy drug cocktail “achieved historically long” PFS and OS compared with chemotherapy alone.

Reguart agreed. “If you look at the progression-free survival, for the first time we reached 7 months. That hasn't been reached before. But what's really striking is the 12-month median overall survival” of more than 19 months. She noted that two earlier phase II trials—SALUTE and GOIRC—which examined another angiogenesis inhibitor, bevacizumab, with chemotherapy in ES-SCLC, yielded no OS advantage.

However, Reguart pointed out that the relative efficacy of the benmelstobart combination “cannot be inferred” from the new trial because it didn't include an immunotherapy plus chemo­therapy treatment arm. In addition, OS data are not mature; longer follow- up is needed, she said, to confirm estimates of effectiveness. The study was conducted only in China and lacked a heterogenous patient population, another limitation of the trial.

Might the findings soon change practice? “Potentially,” Reguart said, “at least in China.” –Suzanne Rose

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