The addition of immunotherapy to frontline platinum-based chemotherapy represents a major advance in treating extensive-stage small cell lung cancer (ES-SCLC). Maintaining longer responses while preserving quality of life remains a critical goal. At a recent 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), which evaluated maintenance therapy with lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq).
The IMforte trial enrolled 660 patients with ES-SCLC who had no prior systemic therapy, no CNS metastases, and good performance status. All patients received four cycles of induction therapy with atezolizumab combined with carboplatin and etoposide. After this induction phase, 483 patients who achieved complete response, partial response, or stable disease were randomly assigned to the maintenance phase. Patients with disease progression or worsened performance status were excluded from randomization. During maintenance, patients received either lurbinectedin plus atezolizumab or atezolizumab alone, continued until disease progression without crossover.
Baseline characteristics were well balanced between treatment arms. Approximately 50% of patients receiving lurbinectedin plus atezolizumab were younger than 65, compared to 37% in the atezolizumab-only group. Around 40% of patients in both arms had liver metastases, indicating a high disease burden. Other factors, including ECOG performance status and lactate dehydrogenase levels, were also balanced. Response rates following induction were similar, with 87% in the combination arm and 88% in the atezolizumab arm achieving either complete or partial responses.
The trial met its primary endpoints of progression-free survival (PFS) and overall survival (OS). Median PFS from randomization was 5.4 months for patients receiving lurbinectedin plus atezolizumab, compared to 2.1 months with atezolizumab alone, representing a 46% reduction in the risk of progression or death (HR 0.54; 95% CI, 0.43-0.67; P < .0001). When including the induction phase, the total median PFS reached approximately 8.4 months. The PFS benefit was evident early and sustained beyond 12 months, with 20.5% of patients progression-free at 12 months on combination therapy versus 12% with atezolizumab alone.
Overall survival was also improved, with a median OS of 13.2 months for the combination maintenance group versus 10.6 months for atezolizumab alone, translating to a 27% reduction in mortality risk (HR 0.73; 95% CI, 0.57-0.95; P = .0174). Adding the induction therapy duration, median survival reached 16.4 months, an encouraging result in this patient population. Survival curves demonstrated a clear divergence at 12 months, with 56% of patients alive on combination treatment compared to 44% on atezolizumab alone, suggesting a sustained benefit for some patients.
The data indicate that maintenance therapy with lurbinectedin plus atezolizumab deepens and prolongs response following initial chemoimmunotherapy, offering improved durability for patients with ES-SCLC. This approach holds promise for enhancing long-term outcomes in a disease historically associated with poor survival.
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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