Chemoradiation with concurrent and consolidation atezolizumab did not improve survival in limited-stage small cell lung cancer (LS-SCLC), suggesting that “timing matters when adding immunotherapy to chemoradiation,” according to a presentation at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting.
The results of the phase 3 NRG Oncology/Alliance LU005 trial, which also showed that twice-daily radiation treatments have greater survival benefits than once-daily radiation, were presented as a late-breaking abstract during the 2024 ASTRO Annual Meeting.
The research “comes on the heels of a recent study showing immunotherapy given after radiation and chemotherapy are completed can increase overall survival” in LS-SCLC, ASTRO officials said in a news release. Therefore, NRG Oncology/Alliance LU005 trial investigators evaluated if there would be a similar benefit from delivering the treatments concurrently.
“The introduction of immunotherapy marked the first significant breakthrough in treating small cell lung cancer treatment in decades. Now, we see that if you give immunotherapy concurrently with chemoradiation, it does not yield the same survival benefit as it does when we add it after standard treatment,” said Kristin Higgins, MD, the principal investigator of the trial, radiation oncologist, and professor and chief clinical officer at City of Hope Cancer Center in Atlanta. “This seemingly small difference in the timing of when the drug is delivered has a very significant impact on the results. At the same time, we found that changing the way you deliver radiation — giving it twice daily — improved survival rates compared to the once daily approach.”
Dr. Higgins and colleagues randomized 544 patients at centers across the United States (n=500) and Japan (n=44) to receive standard chemoradiation with or without atezolizumab immunotherapy. Patients received radiation therapy twice daily for a total dose of 45 Gy (47.2%) or once daily for a dose of 66 Gy (52.8%) as well as 4 cycles of concurrent chemotherapy.
Patients receiving treatment in the experimental arm of the trial received atezolizumab every 3 weeks beginning at the start of radiation for a maximum of 1 year. At the discretion of the investigator, prophylactic cranial irradiation was prescribed for patients who showed a complete or near-complete response to chemoradiation. The median follow-up for the second planned interim analysis was 21 months.
“Contrary to expectations, concurrent treatment with atezolizumab and chemoradiation did not improve survival rates compared to standard care,” ASTRO officials said in the news release.
The 1-year overall survival (OS) rate was 82.6% in patients receiving chemoradiation alone, higher than the rate of 80.2% in patients receiving concurrent chemoradiation and atezolizumab. The 2-year OS rate was 62.9% in patients receiving chemoradiation alone, which was also higher than the rate of 58.6% in those receiving concurrent chemoradiation and atezolizumab. The 3-year OS rates were 50.3% and 44.7%, respectively.
The median OS was over 6 months longer in patients receiving chemoradiation alone (39.5 months), compared with 33.1 months in those who received concurrent chemoradiation and atezolizumab (hazard ratio [HR], 1.1, 95% CI,11.3-18.2).
Dr. Higgins explained the implications of these findings, which showed reduced OS with concurrent chemoradiation and atezolizumab.
“We know that radiation suppresses the immune system to a certain degree in the immediate sense, and immunotherapy relies on the immune system to be effective,” Dr. Higgins said. “Adding these drugs after you give radiation can make the immunotherapy more potent, but you have to allow the immune system time to recover to really see the two work well together.”
The data on progression-free survival (PFS) did not show any benefit with the addition of atezolizumab to chemoradiation, as the median PFS was 11.5 months with atezolizumab, compared to 12 months without. Adding immunotherapy to chemoradiation also did not improve distant metastasis-free survival (13.2 vs 16.8 months, respectively).
However, the study showed there was a benefit to giving radiation twice daily instead of once daily, regardless of the study arm. In both groups, patients who received twice-daily radiation had a median OS of 35.4 months, compared to 28.3 months in those receiving radiation once daily (HR, 1.44, 95% CI1.10-1.89).
“While this wasn’t the primary endpoint of the study, we see clearly that patients receiving radiation for small cell lung cancer do better when you treat them twice daily,” Dr. Higgins stated. “Many doctors and patients may find twice daily radiation more cumbersome, but these data show giving radiation in a more compact way is beneficial for survival.”
Source: ASTRO
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