WASHINGTON– Timing matters when it pertains to integrating immunotherapy with chemoradiation in limited-stage little cell lung cancer (SCLC), according to the stage 3 NRG-LU005 trial provided at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting.
Detectives did not discover a substantial survival advantage amongst clients who got atezolizumab all at once with chemoradiation compared to those who got chemoradiation alone.
The current findings follow those from the ADRIATIC trial, which discovered that beginning durvalumab, another configured death-ligand 1 inhibitor, numerous weeks after completion of chemoradiation extended mean total survival by 22.5 months over chemoradiation alone– 56 months vs 33.5 months– in limited-stage SCLC.
NRG-LU005’s primary detective Kristin Higgins, MD, did not believe the survival results in between the 2 trials varied due to the fact that durvalumab works much better than atezolizumab; both have strong records in SCLC. Rather, radiation– a recognized immunosuppressive– most likely tamped down the immune action required for atezolizumab to work, showing that the body immune system might need time to recuperate from radiation before providing immunotherapy, Higgins discussed.
The takeaway is that offering immunotherapy simultaneously with chemoradiation “is not the method to go,” stated Higgins, a radiation oncologist at City of Hope Cancer Center Atlanta, Newnan, Georgia. “We require to provide it after conclusion of chemoradiation.”
Research study discussant Kenneth Rosenzweig, MD, chair of radiation oncology at Mount Sinai School of Medicine, New York City, concurred that “the timing of immunotherapy is vital.”
In the present open-label, randomized research study, clients had actually gotten one cycle of chemotherapy (platinum/etoposide) before trial registration and were then randomized 1:1 to concurrent chemoradiation (n = 270) or concurrent chemoradiation plus atezolizumab 1200 mg intravenous (n = 274).
Clients had Tx-4, N0-3, M0 illness and were stratified by chemotherapy (cisplatin or carboplatin), radiation fractionation schedule (66 Gy daily vs 45 Gy two times daily), sex, and efficiency status (0-1 vs 2).
Amongst clients getting atezolizumab, the representative was provided every 3 weeks for an optimum of 17 cycles (or about 1 year) up until development or excruciating negative effects. Atezolizumab treatment started throughout the second of 4 cycles of chemotherapy, the very same point when thoracic radiation started. In the control arm, clients got chemoradiation followed by observation.
At 3 years, the total survival rate was 44.7% in the atezolizumab group vs 50.3% in the control arm. Typical total survival had to do with 6 months much shorter in the atezolizumab group– 33.1 months vs 39.5 months in the control group– however the distinction was not substantial (threat ratio [HR]1.11; 95% CI, 0.85-1.45).
Typical progression-free survival was comparable in both groups– 12 months with atezolizumab vs 11.5 months without. The cumulative occurrence of regional failure at 2 years was 13.1% with atezolizumab vs 14.4% without (HR, 0.84; 95% CI, 0.50-1.40). A total or partial reaction was attained in about 59% of both groups.
Grade 3 or greater pneumonitis was more widespread in the atezolizumab group (5.6% vs 3.1%),