Immunotherapy Plus Chemoradiation Improves NSCLC Outcomes

New real-world evidence on non–small cell lung cancer (NSCLC) aligns with the results of a 2017 clinical trial.

New data from more than 20,000 patients with stage III lung cancer suggest that immunotherapy after chemotherapy and radiation can improve outcomes. This study’s findings confirmed the results of the 2017 PACIFIC trial and show clinicians are achieving success despite the timing of immunotherapy falling outside that study’s protocols.

The results of the present study were reported in JAMA Network Open.

Only about 1 in 5 patients with stage III non–small cell lung cancer (NSCLC) survives 5 years, but the PACIFIC trial findings suggested patients with unresectable tumors had better progression-free survival when they were given the anti–programmed death ligand 1 (PD-L1) antibody durvalumab (Imfinzi) following chemoradiation. The trial led to the drug’s FDA approval.

However, the present study’s authors said it remains unknown whether community oncologists are achieving similar favorable results outside of the trial setting, noting that clinical trials tend to include healthier patients, meaning most patients with NSCLC would not qualify for trials.

“Furthermore, patients in the general population may face logistical challenges or socioeconomic disadvantages that impair their ability to comply fully with intended treatment or follow-up appointments,” they wrote.

The investigators turned to the National Cancer Database, which is believed to include about 70% of new lung cancer diagnoses in the United States. They tracked patients who received a clinical stage III NSCLC diagnosis between 2015 and 2017 who were treated with chemotherapy and radiation. They then compared the outcomes among propensity-matched cohorts of patients who received immunotherapy and those who did not. Follow-up was through the end of 2018.

A total of 23,811 patients were identified who met the criteria. Only 1297 (5.4%) received immunotherapy, but they had reduced mortality (HR, 0.74; 95% CI, 0.67-0.82; P < .001). Immunotherapy also led to improved 3-year survival compared with those who did not receive immunotherapy (52% vs 44%).

“These findings support the PACIFIC trial findings,” the authors wrote. “The magnitude of the overall survival benefit of immunotherapy is similar to the mortality reduction identified in the PACIFIC trial.” That trial had a 32% reduced mortality risk when immunotherapy was included vs when it was not, they noted.

Sixteen percent of patients in the present study’s immunotherapy cohort were older than 75 years, and 16% had medical comorbidities, suggesting the benefits of immunotherapy extend to a wider population than was included in the study.

The investigators also noted, however, that 65% of the patients in their data set received treatment different from study protocols. In PACIFIC, protocols mandated the start of immunotherapy within 6 weeks of the completion of radiation and a subset analysis suggested starting within 2 weeks was ideal.

The present authors said their data did not identify a significant advantage to early immunotherapy, and they said patients experienced benefits even when the timing of immunotherapy did not line up with the trial’s suggested time frame.

“Our results suggest there may be flexibility in the time to initiate immunotherapy after the completion of radiation,” they said.

The authors noted that given the nature of their data set, certain information was not available about patients, such as smoking status and estimated glomerular filtration rate. They also noted that certain factors, such as whether a tumor is resectable or not, are subjective.

Still, they concluded the benefits of immunotherapy after chemoradiation extend to a general population. They said taking advantage of the apparent flexibility in immunotherapy timing could help alleviate barriers to immunotherapy in some patients.


Pichert MD, Canavan ME, Maduka RC, et al. Immunotherapy after chemotherapy and radiation for clinical stage III lung cancer. JAMA Netw Open. 2022;5(8):e2224478. doi:10.1001/jamanetworkopen.2022.24478

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