The NRG Oncology/Alliance LU005 trial, a study involving over 500 patients in the U.S. and Japan, revealed that the addition of atezolizumab (Tecentriq) to standard chemoradiotherapy (CRT) did not significantly improve overall survival in patients with limited-stage small-cell lung cancer (LS-SCLC). This finding challenges the integration of immunotherapy in this specific treatment approach for LS-SCLC.
The study, presented at the 2024 American Society for Radiation Oncology (ASTRO) annual meeting, tested standard CRT with or without atezolizumab. All patients received radiotherapy either twice daily to a total dose of 45 Gy or once daily to a dose of 66 Gy, along with four cycles of concurrent chemotherapy. Patients in the atezolizumab arm received the agent every 3 weeks, starting at the beginning of radiotherapy, for up to 1 year. Prophylactic cranial RT was administered at the investigator's discretion for patients with a complete or near-complete response to CRT. The median follow-up for the second planned interim analysis was 21 months.
Key Findings from the Trial
Kristin Higgins, MD, of City of Hope Cancer Center Atlanta, presented the main findings at an ASTRO press briefing. The primary endpoint of the study was overall survival (OS). "There was no significant difference in survival for patients who received concurrent CRT with atezolizumab compared with the control arm," Higgins stated. The median OS for the control arm was 39 months, while it was 33 months for the atezolizumab arm. Median progression-free survival was 11.5 months for the control arm and 12 months for the atezolizumab arm.
An interesting observation was related to the radiation therapy schedule. Patients who received twice-daily radiation had improved survival compared to those who received once-daily radiation, with a median OS of 35 months versus 28 months, respectively.
Implications and Expert Commentary
Higgins emphasized that concurrent atezolizumab did not improve survival for patients with LS-SCLC compared to standard CRT. She suggested that twice-daily RT might be associated with improved survival compared to daily RT and should be considered the optimal RT choice for patients with LS-SCLC.
Kenneth Rosenzweig, MD, of Icahn School of Medicine at Mount Sinai, offered an expert perspective, noting the critical importance of immediate treatment initiation in this patient population. He highlighted two key findings: the timing of immunotherapy is crucial, and radiation therapy to major lymph nodes and a large blood volume might affect the effectiveness of immunotherapy. Rosenzweig also pointed out that while twice-daily RT can be inconvenient, its potential benefits warrant further consideration, especially with modern techniques to limit toxicity.
Context of SCLC Treatment
LS-SCLC has historically been challenging to treat, with the concurrent CRT backbone, plus or minus prophylactic cranial irradiation, remaining the standard for the past 30 years. While there have been recent successes in extensive-stage SCLC (ES-SCLC) with the addition of immunotherapy to chemotherapy, the NRG Oncology/Alliance LU005 trial indicates that this approach does not translate to improved outcomes in limited-stage disease. The trial underscores the need for continued research to optimize treatment strategies for LS-SCLC and to better understand the interplay between radiation therapy and immunotherapy.
