Immunotherapy Timing and Radiation Strategies Show Mixed Results in Lung Cancer Trials
Recent studies reveal immunotherapy failed to improve survival in small-cell lung cancer when combined with chemoradiation, while timing of immunotherapy after radiation therapy affects outcomes in non-small cell lung cancer patients.
Immunotherapy given during and after chemoradiation did not improve survival for study participants with limited-stage, small-cell lung cancer (SCLC) according to the results of an international clinical trial, NRG-LU005, led by NRG Oncology in collaboration with the Alliance for Clinical Trials in Oncology. The results are published in the Journal of Clinical Oncology.
The trial did not meet its primary endpoint as the addition of the immunotherapy agent atezolizumab to chemotherapy and radiation did not significantly improve survival for those with limited-stage SCLC. However, twice-daily radiation therapy was associated with improved survival in this population.
The LU005 study enrolled 544 patients between May 2019 and December 2023 across 218 sites in the United States and Japan. Participants were assigned to receive either standard concurrent chemoradiation alone or chemoradiation plus atezolizumab intravenously every three weeks starting with the first study cycle, which was the second cycle of chemotherapy.
Thoracic radiation was delivered using one of two schedules: 45 Gy administered twice daily over three weeks, or 66 Gy administered once daily over six-and-a-half weeks. The primary endpoint of the study was overall survival, with key secondary endpoints including progression-free survival, distant metastasis-free survival, objective response rate, local control, and safety.
The addition of atezolizumab did not improve progression-free or overall survival. The median overall survival was 36.1 months in the chemoradiation-alone arm and 31.1 months in the chemoradiation plus atezolizumab arm. Median progression-free survival was 11.4 months for chemoradiation alone and 12.1 months for the atezolizumab group. The 36.1-month median overall survival in the standard chemoradiation arm represents one of the longest survival outcomes ever reported in a randomized study in people with limited-stage SCLC.
An interesting finding in LU005 was the consistent survival benefit associated with twice-daily radiation therapy. In the chemoradiation-alone arm, patients receiving once-daily radiation had a 51 percent higher risk of death compared to those treated twice daily. A similar trend favoring twice-daily radiation was also observed in the atezolizumab arm.
In patients with stage III unresectable non-small cell lung cancer (NSCLC), the use of intermediate dose escalation (IDE) of radiotherapy (RT) may not provide benefit to those who have received immunotherapy more than 6 weeks after having definitive concurrent chemoradiation (dcCRT). These findings, based on an analysis of data from the National Cancer Database (NCDB), were published in Frontiers in Oncology.
The study included NCDB data for adult patients with unresectable, stage III NSCLC who underwent dcCRT. The researchers compared the use of standard RT doses of 57 to 63 Gy with the use of IDE (RT doses of 64-74 Gy), during the pre-immunotherapy era (2004-2016) and in the immunotherapy era (2017-2020), in assessments of overall survival (OS) and all-cause mortality.
In this population, 47,315 patients had been diagnosed in the pre-immunotherapy era and received dcCRT only. Another 4749 patients, diagnosed later, had received dcCRT and immunotherapy. Median age at diagnosis was 67 years in both groups.
Among patients who had received dcCRT without immunotherapy (in the pre-immunotherapy era), those who received the standard RT dose (57-63 Gy) demonstrated statistically significantly worse all-cause mortality compared with patients who received IDE (hazard ratio [HR], 1.09; 95% CI, 1.07-1.12; P <.001). Median survival times were 19.7 months and 21.2 months, respectively (P <.0001).
For patients treated in the immunotherapy era, a standard RT dose was also associated with worse all-cause mortality than observed with IDE (HR, 1.17; 95% CI, 1.03-1.33; P =.02). The survival benefit with IDE, however, was limited only to patients who had initiated immunotherapy within 6 weeks following completion of RT (HR, 1.26; 95% CI, 1.05-1.6; P =.01).
In the immunotherapy era, all-cause mortality rates were similar for patients receiving either a standard RT dose or IDE in analyses of those who started immunotherapy between 7 and 10 weeks after completing RT (HR, 1.13; 95% CI, 0.88-1.45; P =.35) or who started immunotherapy beyond 10 weeks after RT completion (HR, 0.74; 95% CI, 0.51-1.07; P =.11).