Second-line tislelizumab + anlotinib + chemo shows potential to improve ES-SCLC survival

A treatment regimen combining tislelizumab, anlotinib, and two cycles of irinotecan in the second-line setting demonstrates favourable efficacy and safety in patients with extensive-stage small cell lung cancer (ES-SCLC), according to the results of the single-arm phase II ESTAIL study.

ESTAIL met its primary endpoint, with an objective response rate (ORR) of 50 percent over a median follow-up of 9.6 months. Most patients had partial response (50 percent), and 37.5 percent had stable disease, reported first study author Dr Xian Cheng from the Guangdong Hospital of Traditional Chinese Medicine in Guangzhou, China. [WCLC 2024, abstract MA17.09]

The disease control rate was 87.5 percent, and the median duration of response was 5.72 months.

When examining specific subgroups, the regimen demonstrated encouraging antitumour efficacy in patients with brain metastases (ORR, 60 percent) and those who had progressed after first-line treatment with platinum-doublet chemotherapy (platinum/etoposide or epirubicin/cyclophosphamide) alone (ORR, 56.5 percent) or in combination with a PD-L1 inhibitor (ORR, 33.3 percent), Cheng noted.

Survival outcomes

The median progression-free survival (PFS) was 7.1 months (95 percent confidence interval [CI], 3.06–9.89), with a 6-month PFS rate of 53.2 percent. PFS data were consistent in the subgroup of patients with brain metastasis (median PFS 7.1 months, 6-month PFS 51.6 percent).

The median overall survival (OS) was 7.5 months (95 percent CI, 5.29–11.0), and the 6-month OS rate was 65.4 percent. Exploratory analysis showed that the median OS from first-line treatment to data cutoff was 17.2 months (95 percent CI, 11.9–20.0).

Safety

“The overall safety of the regimen combining tislelizumab, anlotinib, and two cycles of irinotecan was manageable,” Cheng said.

In total, 25 percent of patients had grade 3 or higher treatment-related AEs, including decreased platelet count (12.5 percent) and decreased neutrophil count (9.3 percent). Meanwhile, 6.25 percent of patients had grade 3 or higher immune-related AEs, such as hyperglycaemia (3.1 percent) and hyperthyroidism (3.1 percent).

Taken together, these data indicate that tislelizumab combined with anlotinib and two cycles of irinotecan may provide a new treatment strategy in the second-line setting to improve the clinical outcome in ES-SCLC, Cheng pointed out.

ESTAIL included 32 adult patients (median age 64 years, 90.6 male) with pathologically confirmed ES-SCLC, who had progressed or relapsed (≤6 months) after first-line treatment with EP or EC alone or in combination with PD-L1 inhibitor. These patients were treated with tislelizumab (200 mg every 3 weeks) plus anlotinib (10 mg every day for 14 days, then every 3 weeks thereafter) and irinotecan (100 mg/m² intravenously at day 1 and day 8, then every 3 weeks thereafter) for up to two cycles, followed by tislelizumab plus anlotinib maintenance therapy.