Primary completion results for a Phase 3 study evaluating atezolizumab in combination with lurbinectedin for maintenance therapy in extensive-stage small-cell lung cancer (ES-SCLC) were posted on ClinicalTrials.gov on 2024-07-29. The combination therapy demonstrated improved outcomes, with a median progression-free survival (PFS) of 5.36 months compared to 2.14 months for atezolizumab alone, and a median overall survival (OS) of 13.24 months versus 10.64 months.
Background
The Phase 3 study investigated atezolizumab, an immunotherapy, in combination with lurbinectedin for maintenance therapy in participants with extensive-stage small-cell lung cancer (ES-SCLC). Participants had previously completed first-line induction therapy consisting of carboplatin, etoposide, and atezolizumab, and had an ongoing response or stable disease. The trial aimed to assess if adding lurbinectedin to atezolizumab maintenance therapy could improve outcomes compared to atezolizumab alone.
Trial design
The Phase 3, open-label, randomized, multicenter study (NCT05091567) enrolled 660 participants with extensive-stage small-cell lung cancer (ES-SCLC). The study compared maintenance therapy with lurbinectedin in combination with atezolizumab against atezolizumab alone. Participants were randomized after completing 4 cycles of first-line induction therapy with carboplatin, etoposide, and atezolizumab, provided they had an ongoing response or stable disease per RECIST v1.1 criteria.
Key results
The trial results demonstrated improved efficacy for the combination arm:
- Independent Review Facility (IRF) - Assessed Progression Free Survival (PFS): The median PFS was 5.36 months (95% Confidence Interval: 4.24 months) for the Atezolizumab + Lurbinectedin arm, compared to 2.14 months (95% Confidence Interval: 1.64 months) for the Atezolizumab arm. A stratified analysis showed a Hazard Ratio (HR) of 0.54 (95% CI: 0.43-0.67) with a p-value of 0.0001.
- Overall Survival (OS): The median OS was 13.24 months (95% Confidence Interval: 11.89 months) for the Atezolizumab + Lurbinectedin arm, versus 10.64 months (95% Confidence Interval: 9.49 months) for the Atezolizumab arm. A stratified analysis yielded an HR of 0.73 (95% CI: 0.57-0.95) with a p-value of 0.0174.
- Investigator-assessed PFS: The median PFS was 5.36 months (95% Confidence Interval: 4.30 months) for the Atezolizumab + Lurbinectedin arm, compared to 2.73 months (95% Confidence Interval: 2.53 months) for the Atezolizumab arm. The Hazard Ratio was 0.55 (95% CI: 0.45-0.68).
- Confirmed Objective Response Rate (ORR) as Determined by the IRF: The ORR was 19.4 percentage of participants (95% Confidence Interval: 13.85 percentage of participants) for the Atezolizumab + Lurbinectedin arm, compared to 10.4 percentage of participants (95% Confidence Interval: 6.40 percentage of participants) for the Atezolizumab arm. The difference in ORR was 8.99 (95% CI: 1.07-16.9).
- Duration of Response (DOR) as Determined by the IRF: The median DOR was 9.00 months for the Atezolizumab + Lurbinectedin arm, compared to 5.62 months for the Atezolizumab arm.
What this means
The results from this Phase 3 study suggest that adding lurbinectedin to atezolizumab maintenance therapy significantly improves key efficacy outcomes for patients with extensive-stage small-cell lung cancer (ES-SCLC) who have responded to initial induction therapy. The observed increase in median progression-free survival by over 3 months (5.36 months vs 2.14 months) and median overall survival by over 2.5 months (13.24 months vs 10.64 months) indicates a clinically meaningful benefit. These findings could support the use of this combination as a new maintenance strategy, potentially extending the time patients live without disease progression and overall survival in this aggressive cancer type.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The primary completion results for the study NCT05091567, titled "A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer", were posted on 2024-07-29 on clinicaltrials.gov.