A combination therapy of Roche's immunotherapy Tecentriq (atezolizumab) and Zepzelca (lurbinectedin) has demonstrated significant survival benefits for patients with metastatic small cell lung cancer (SCLC), according to new Phase 3 clinical trial data released Thursday.
The large-scale trial enrolled 660 patients with metastatic SCLC and evaluated the efficacy of using Tecentriq and Zepzelca in combination as maintenance therapy compared to Tecentriq alone. The findings will be presented at the American Society of Clinical Oncology's (ASCO) annual meeting on June 2.
Significant Improvement in Survival Metrics
Among the 483 participants who progressed to the maintenance phase following initial treatment with chemotherapy and Tecentriq, those receiving the combination therapy showed markedly improved outcomes. The median progression-free survival reached 5.4 months for patients given Tecentriq plus Zepzelca, compared to just 2.1 months in the Tecentriq monotherapy group.
More importantly, the combination therapy extended median overall survival to 13.2 months versus 10.6 months with Tecentriq alone, representing a 2.6-month improvement in this difficult-to-treat cancer type.
These results build upon the current standard of care. The FDA has previously approved four cycles of Tecentriq plus chemotherapy as first-line therapy for metastatic SCLC, followed by Tecentriq alone as maintenance. That regimen demonstrated a median overall survival of 12.3 months in earlier studies.
Safety Considerations
The improved efficacy of the combination therapy came with increased toxicity. Side effects were reported in 84% of patients in the combination arm compared to 40% in the Tecentriq-only group. The incidence of severe adverse events was also higher with the combination.
Two patients receiving the combination therapy died from treatment-related complications (sepsis and febrile neutropenia), while one patient on Tecentriq monotherapy died from sepsis.
Expert Perspective
Julie Gralow, ASCO's chief medical officer, commented on the findings during a press call: "We would anticipate that it would be moved into the first-line maintenance setting. Progression-free survival is still quite low in both arms, and we need to work on additional ways of advancing this even further."
She characterized the results as "a small next step" in the treatment landscape for SCLC, acknowledging both the progress made and the continued challenges in managing this aggressive cancer type.
Background on Zepzelca
Zepzelca received conditional FDA approval in 2020 for treating patients with SCLC whose disease has progressed after platinum-based chemotherapy. This approval was based on tumor response rates and treatment duration, with confirmatory trials still needed.
The drug has an interesting origin story, having been developed by Spanish biotech PharmaMar from marine-derived compounds. Zepzelca is a synthetic version of a substance found in colonial ascidians, a type of marine invertebrate.
Jazz Pharmaceuticals, which licensed U.S. rights to Zepzelca in 2019 and later added Canadian marketing rights, reported $320 million in Zepzelca sales last year. The company paid PharmaMar approximately $60 million in royalties.
Implications for Treatment Paradigm
Maintenance therapy plays a crucial role in SCLC management, helping to delay cancer recurrence or stabilize disease after initial treatment response. The Zepzelca-Tecentriq combination represents a potentially important advancement in maintenance strategies.
Given the aggressive nature of SCLC and limited treatment options, these results may influence clinical practice guidelines and provide oncologists with an additional therapeutic approach for patients with this challenging malignancy.
The findings are particularly significant considering that SCLC accounts for approximately 15% of all lung cancer cases and is characterized by rapid growth, early metastasis, and poor prognosis compared to non-small cell lung cancer.
