Immunotherapy after chemotherapy and radiation provides a survival benefit for patients with unresectable, stage III non-small cell lung cancer (NSCLC), according to real-world data published in JAMA Network Open

Researchers noted that the PACIFIC trial ( Identifier: NCT02125461) established a role for the use of immunotherapy after chemoradiation in this patient population. 

However, the general population of patients with unresectable, stage III NSCLC in the United States may differ from patients enrolled in the PACIFIC trial. 

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To assess real-world outcomes of immunotherapy after chemoradiation, the researchers analyzed data from the National Cancer Database. 

The analysis included 23,811 patients who were newly diagnosed with unresectable, stage III NSCLC between 2015 and 2017. The median age at baseline was 66 (range, 59-72) years, 43.9% of patients were women, and 84.3% were White. 

All patients received chemotherapy and radiation, and 1297 patients (5.4%) received immunotherapy as well. Of the immunotherapy recipients, 16.5% were 75 years of age or older and 16.1% had a Charlson-Deyo Comorbidity Index score of 2-3.

The proportion of patients who received immunotherapy increased over time, from less than 1% in 2015 to 15% in 2017. 

About two-thirds (64.2%) of immunotherapy recipients had treatment that differed from the PACIFIC trial protocol. Specifically, 56.4% of patients started immunotherapy more than 42 days after radiation ended, 12.2% of patients received a lower dose of radiation than was used in the PACIFIC trial (54-66 Gy), and 4.9% received a higher dose. 

Survival Results

In an unadjusted analysis, adding immunotherapy to chemoradiation was associated with superior 3-year survival, compared with chemoradiation alone (52% vs 44%; P <.001). 

In an adjusted analysis, the addition of immunotherapy was still associated with a reduction in mortality (hazard ratio HR, 0.74; 95% CI, 0.67-0.82; P <.001). 

“The magnitude of the overall survival benefit of immunotherapy is similar to the mortality reduction identified in the PACIFIC trial (HR, 0.68; 95% CI, 0.47-0.997),” the researchers wrote. 

The survival advantage of immunotherapy persisted when it was initiated up to 12 weeks after radiation (HR, 0.75; 95% CI, 0.61-0.92). 

However, for those patients who received radiation doses outside of the PACIFIC protocol range (54-66 Gy), there was no significant survival advantage with immunotherapy. 

The survival advantage was only significant for patients who received a dose of 60 Gy (HR, 0.71; 95% CI, 0.62-0.81) or 61-66 Gy (HR, 0.70; 95%CI, 0.57-0.86). The researchers noted, however, that the subset of patients receiving 60 Gy was the largest subset of patients (n=653).

“Overall, the results of this retrospective cohort study suggest that the benefit of immunotherapy after chemoradiation for stage III NSCLC may extend to the general population in the US, including patients who are older and those who are socioeconomically disadvantaged,” the researchers wrote. “There may be flexibility in the multimodality treatment planning, including the time to initiate immunotherapy, which may alleviate barriers to immunotherapy treatment in some patients.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pichert MD, Canavan ME, Maduka RC, et al. Immunotherapy after chemotherapy and radiation for clinical stage III lung cancer. JAMA Netw Open. Published online August 4, 2022. doi:10.1001/jamanetworkopen.2022.24478