Survival benefit with postchemoradiation immunotherapy affirmed

Starting immunotherapy after chemotherapy and radiation for unresectable stage III nonsmall cell lung cancer (NSCLC) prolongs overall survival, regardless of patient age, health, and socioeconomic status, according to a large US study.

In a cohort of 23,811 patients (median age 66 years, 43.9 percent female, 2.4 percent Asian, and 12.3 percent Black), postchemoradiation immunotherapy cut the risk of death by 26 percent as compared with chemotherapy and radiation alone (hazard ratio [HR], 0.74, 95 percent confidence interval [CI], 0.67–0.82; p<0.001). [JAMA Netw Open 2022;5:e2224478]

The 3-year survival in a propensity-matched sample also favoured the addition of immunotherapy (52 percent vs 44 percent; p<0.001).

“These findings support the PACIFIC trial findings. The magnitude of the overall survival benefit of immunotherapy is similar to the mortality reduction identified in the PACIFIC trial (HR, 0.68, 95 percent CI, 0.47–0.997),” the investigators said. [N Engl J Med 2018;379:2342-2350]

“[Our] population study extends the PACIFIC clinical trial findings by associating immunotherapy with a survival benefit in a cohort that included a wide range of patient age (16 percent were older than 75 years), health (16 percent of patients had multiple medical comorbidities), and socioeconomic status (24.5 percent had indicators of socioeconomic disadvantage),” they pointed out.

Not time sensitive

Another important thing to note is that the 833 patients who received immunotherapy (64.2 percent) in the current study were treated in a manner that differed from the PACIFIC trial protocol. There were 221 patients (17.0 percent) received radiation doses outside of the protocol range and 731 patients (56.4 percent) started immunotherapy more than 6 weeks after radiation was completed.

Nevertheless, the survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75, 95 percent CI, 0.61–0.92). Meanwhile, the benefit was not significant among patients who received radiation outside the PACIFIC protocol range (HR, 0.87, 95 percent CI, 0.69-1.01).

The findings above suggest that the best time to start immunotherapy for patients who have just completed chemoradiation may not exist, as there appears to be some flexibility in the timing of initiation, according to the investigators.

“More specifically, the PACIFIC trial dictated that immunotherapy should be initiated within 6 weeks of the completion of radiation. This timeframe was chosen because of the perception that the initiation of immunotherapy is time sensitive, and a number of contemporary trials have also included similar time-to-initiation restrictions,” they added. [https://clinicaltrials.gov/ct2/show/NCT04513925; https://clinicaltrials.gov/ct2/show/NCT03693300; https://clinicaltrials.gov/ct2/show/NCT04364048]

However, the PACIFIC trial treatment recommendations are unlikely to be fully complied with by all patients in a clinical setting, the investigators noted.

“Some patients struggle with chemoradiation for stage III NSCLC … and therefore a percentage of patients may require additional time to recover from chemoradiation prior to starting immunotherapy,” they said. “In the current study, findings would suggest a delay in initiation beyond 6 weeks is not necessarily a contraindication to immunotherapy.”

The investigators called for additional study to establish the utility of immunotherapy in stage III NSCLC in a clinical setting.