The addition of immunotherapy to frontline platinum-based chemotherapy marked a significant advancement in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Maintaining longer responses in patients receiving chemoimmunotherapy while preserving quality of life represents another important development in this field. At a recent live Community Case Forum in Saddle Brook, New Jersey, Joshua K. Sabari, MD, assistant professor at NYU Grossman School of Medicine, discussed the phase 3 IMforte trial (NCT05091567) evaluating maintenance therapy with lurbinectedin (Zepzelca) and atezolizumab (Tecentriq).
The IMforte trial enrolled 660 patients with ES-SCLC who had not received prior systemic therapy, had no CNS metastases, and maintained good performance status. All patients underwent an induction phase consisting of four cycles of atezolizumab combined with carboplatin and etoposide. Following induction, 483 patients who achieved complete response, partial response, or stable disease were eligible for randomization to the maintenance phase. Patients with disease progression or deterioration in performance status were excluded from randomization.
During maintenance, patients were assigned to receive either lurbinectedin at 3.2 mg/m2 plus atezolizumab or atezolizumab alone until disease progression, with no crossover permitted. The trial’s primary endpoints were progression-free survival (PFS) and overall survival (OS).
Baseline characteristics after randomization showed balanced demographics and disease features. About 50% of patients in the combination arm were under 65 years of age compared to 37% in the atezolizumab-alone arm. Both groups had similar sex distribution. Notably, liver metastases were present in 42% of patients receiving lurbinectedin/atezolizumab and 39% receiving atezolizumab alone. ECOG performance status and lactate dehydrogenase levels, markers of disease burden, were well balanced between arms. Median time from cycle 1 to induction completion was 3.2 months in both groups. Pre-maintenance response rates were comparable, with 87% in the combination arm and 88% in the atezolizumab-alone arm achieving complete or partial responses.
Following randomization, median PFS was 5.4 months for patients receiving maintenance lurbinectedin and atezolizumab compared with 2.1 months for those receiving atezolizumab alone, representing a 46% reduction in risk of progression or death (hazard ratio [HR] 0.54; 95% CI, 0.43-0.67; P < .0001). When including the induction period, median PFS extended to 8.4 months. The PFS curves showed early and sustained separation, with 20.5% of the combination arm progression-free at 12 months versus 12% in the atezolizumab-alone group. At six months, progression-free rates were 40% versus 18%, respectively.
Median overall survival was 13.2 months for the combination maintenance group versus 10.6 months for the atezolizumab-alone group, reflecting a 27% reduction in mortality risk (HR 0.73; 95% CI, 0.57-0.95; P = .0174). Including the induction period, median OS reached approximately 16.4 months. Survival curves demonstrated a separation at the 12-month landmark, with 56% of patients alive in the combination arm compared to 44% in the atezolizumab-alone arm. These results suggest that combining lurbinectedin with immunotherapy deepens and prolongs response duration in ES-SCLC, offering a durable clinical benefit.
The IMforte trial findings underscore the value of maintenance therapy with lurbinectedin plus atezolizumab following frontline chemoimmunotherapy in ES-SCLC, supporting its role in extending progression-free and overall survival.
Disclosure: Dr. Sabari has received consulting or advisory fees from AstraZeneca, Pfizer, Regeneron, Medscape, Takeda, Janssen, Genentech/Roche, Mirati Therapeutics, AbbVie, Loxo/Lilly, and Sanofi, and institutional support from Janssen, Loxo/Lilly, Mirati Therapeutics, and Regeneron.
Reference: Paz-Ares L, Borghaei H, Liu SV, et al. Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2025;405(10495):2129-2143. doi:10.1016/S0140-6736(25)01011-6
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