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SINGAPORE -- Adding the investigational combination of PD-L1 inhibitor benmelstobart and antiangiogenic tyrosine kinase inhibitor anlotinib to first-line chemotherapy significantly improved survival in extensive-stage small-cell lung cancer (ES-SCLC) Chinese researchers found.

At a median follow-up of 14 months, median progression-free survival (PFS) was 6.9 months with the combination compared with 4.2 months with chemotherapy plus placebo (HR 0.32, 95% CI 0.26-0.41, P<0.0001), reported Ying Cheng, MD, of the Jilin Cancer Hospital in Changchun, China.

Overall survival (OS), meanwhile, reached 19.3 months versus 11.9 months, respectively (HR 0.61, 95% CI 0.46-0.79, P=0.0002), findings presented at the World Conference on Lung Cancer in Singapore showed.

"The addition of an antiangiogenic agent to immunotherapy in the first-line treatment of ES-SCLC resulted in the historically longest progression-free survival and overall survival, supporting the use of immunochemotherapy plus anlotinib as a new treatment option for this patient population," said Cheng.

Discussant Noemí Reguart, MD, PhD, of the Hospital Clínic Barcelona in Spain, called the OS results "striking," and said the results are "potentially" practice changing, "in China at least."

However, she noted that that the relative efficacy of the triple combination over immunochemotherapy can't be inferred since the control arm in this trial did not include immunotherapy, and that more mature data are needed to demonstrate the true estimates of the combination's effectiveness.

Six- and 12-month PFS rates were 59.1% and 27.9% in the combination arm, respectively, and 16.6% and 2.3% with chemotherapy alone. Twelve- and 24-month OS rates of 64.1% and 41.8%, respectively, were seen with the triplet regimen versus 49% and 24.2% with chemotherapy alone.

Subgroup analyses showed that all subgroups demonstrated a PFS and OS benefit with the combination.

Objective response rates were 81.3% in the combination arm and 66.8% with chemotherapy alone, while the durations of response were 5.8 and 3.1 months, respectively.

In explaining the rationale for the study, Cheng explained that while immunochemotherapy has shown promise by extending OS by 2 to 4 months in ES-SCLC, "improving long-term survival remains an unmet need."

"Considering the complexity and heterogeneity of the SCLC microenvironment, we made an advanced design to combine benmelstobart with anlotinib plus standard chemotherapy, aiming to obtain improved efficacy, longer survival benefits, and management safety in ES-SCLC," she said.

The study included 738 patients from 72 participating centers in China who were assigned to three groups.

One-third (246) of the patients (median age 62 years, 85% male) were assigned to receive four cycles of benmelstobart plus anlotinib with etoposide/carboplatin chemotherapy, followed by maintenance therapy of benmelstobart plus anlotinib, while a second group of 247 patients (median age 63 years, 84% male) received four cycles of placebo plus chemotherapy, followed by placebo maintenance therapy.

A third group of patients received four cycles of placebo plus anlotinib and chemotherapy, followed by placebo plus anlotinib maintenance therapy, and were not included in this analysis.

Cheng called the safety profile of the benmelstobart-based regimen "tolerable and manageable."

Treatment-related adverse events (TRAEs) of any grade were experienced by all patients in the combination arm and 99.6% of those treated with chemotherapy alone. Grade ≥3 TRAEs were reported in 93.1% and 87.0% of patients in the two groups, respectively.

TRAEs of any grade leading to dose reductions, discontinuation, or death occurred in 50.4%, 8.5%, and 4.5% of patients in the combination arm, and 23.2%, 2.8%, and 1.6% with chemotherapy alone.

Any-grade immune-related adverse events were reported in 42.7% of patients in triplet arm and 19.1% in the chemotherapy-alone arm.

The most common grade ≥3 TRAEs were decreased neutrophil count, decreased platelet count, and decreased white blood cell count in both arms.

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