Anlotinib plus etoposide/carboplatin improves survival in extensive-stage SCLC

Use of anlotinib combined with etoposide and carboplatin (EC; chemotherapy) as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC) yields a significantly improved progression-free survival (PFS) as well as overall survival (OS) benefits when compared with chemotherapy, according to data from the phase III ETER701 trial presented at ELCC 2024.

“The survival benefits of antiangiogenesis plus chemotherapy is comparable to immunochemotherapy, and the safety profile is tolerable and manageable,” said lead author Ying Cheng, chief physician in the Department of Thoracic Oncology at the JiLin Province Cancer Hospital in Changchun, China.

Patients with ES-SCLC who received anlotinib plus chemotherapy had a median PFS of 5.6 months (95 percent confidence interval [CI], 5.55‒6.83) compared with 4.2 months (95 percent CI, 4.17‒4.24) in those treated with EC (hazard ratio [HR], 0.44, 95 percent CI, 0.36‒0.55; p<0.0001). [Cheng Y, et al, ELCC 2024, abstract 196MO]

At 12 months, the PFS rates were 12.61 percent (95 percent CI, 7.81‒18.60) for the anlotinib arm and 2.29 percent (95 percent CI, 0.56‒6.38) for the EC arm. [www.onclive.com/view/anlotinib-plus-etoposide-and-carboplatin-improves-pfs-in-es-sclc]

OS also improved in both treatment arms, but this benefit did not reach statistical significance. The median OS was 13.27 months (95 percent CI, 11.14‒15.05) in patients treated with anlotinib plus chemotherapy versus 11.89 months (95 percent CI, 10.47‒13.37) in those who received EC (HR, 0.86; 95 percent CI, 0.67‒1.10; p=0.1732).

At 12 months, the OS rates were 54.63 percent (95 percent CI, 46.33‒60.39) for the anlotinib arm and 49.00 percent (95 percent CI, 41.66‒55.93) for the EC arm.

“[The] PFS improvement of anlotinib plus etoposide, carboplatin, [and placebo] did not translate into a statistically significant increase in OS,” Cheng said. [www.onclive.com/view/anlotinib-plus-etoposide-and-carboplatin-improves-pfs-in-es-sclc]

“As anlotinib plus chemoimmunotherapy [etoposide, carboplatin, and benmelstobart] significantly improved PFS and OS, [this suggests] that anlotinib plus chemoimmunotherapy may have a more durable synergistic effect in ES-SCLC,” she added.

With regard to safety, grade 3 or higher treatment-related adverse events (TEAEs) occurred in 94.3 percent of patients in the anlotinib arm and 87.0 percent of those in the EC arm. Grade 5 TEAEs occurred in 2.5 percent and 1.6 percent of patients, respectively.

ETER701

Cheng and her team enrolled a total of 738 patients with ES-SCLC between 18 March 2020 and 18 December 2021. Of these, 245 were randomized to receive anlotinib plus EC plus benmelstobart (a novel PD-L1 inhibitor) and 247 to EC plus placebo for four 21-day cycles. Patients then received maintenance therapy with benmelstobart plus anlotinib or anlotinib plus placebo or EC plus placebo.

PFS, as assessed by the independent review committee, and OS in the intention-to-treat population were the primary endpoints.

“ETER701 is the first randomized phase III trial evaluating anlotinib + etoposide/carboplatin [EC] ± benmelstobart … versus placebo + EC in first-line ES-SCLC therapy,” Cheng said. “A historically longest OS was observed with anlotinib + EC + benmelstobart versus placebo + EC.”