medwireNews: A US National Cancer Database (NCDB) analysis suggests that immunotherapy after chemoradiotherapy for unresectable stage III non-small-cell lung cancer (NSCLC) is associated with an overall survival (OS) benefit in the general US population.
The survival advantage was observed even though nearly two-thirds of the patients were treated differently than in the pivotal PACIFIC trial that was the first to establish a role for immunotherapy in this setting, say the investigators.
They also highlight that the OS benefit was shown “in a cohort that included a wide range of patient age (16% were older than 75 years), health (16% of patients had multiple medical comorbidities), and socioeconomic status (24.5% had indicators of socioeconomic disadvantage).”
Daniel Boffa and colleagues from Yale University School of Medicine in New Haven, Connecticut, USA, identified 23,811 patients included in the NCDB who received chemotherapy plus radiation for stage III NSCLC between 2015 and 2017. Of these, 5.4% received consolidation immunotherapy after chemoradiotherapy.
After adjusting for multiple confounders, such as age, sex, comorbidities, and histology, receipt of immunotherapy was associated with a significantly reduced risk for death, at a hazard ratio (HR) of 0.74.
And Kaplan–Meier analysis of a propensity-matched sample showed that OS at 3 years was significantly better among patients who did versus did not receive immunotherapy, at rates of 52% and 44%, respectively.
The team points out in JAMA Network Open that the treatment of 64.2% of patients given immunotherapy differed from the PACIFIC trial protocol. Specifically, 56.4% of patients started immunotherapy more than 6 weeks after radiotherapy completion and 17.0% received radiation doses outside of the protocol range.
But the OS advantage afforded by immunotherapy was maintained when initiated 7–9 weeks, 10–12 weeks, and more than 12 weeks after radiation, at HRs of 0.70, 0.61, and 0.75, respectively, relative to no immunotherapy.
By contrast, “the advantage of immunotherapy was less clear in patients treated outside the recommended range” of radiation dose (54–66 Gy), say Boffa and co-authors, but caution that the subgroups “may have been underpowered.” A significant OS benefit with immunotherapy was only observed for individuals who received doses of 60 Gy or 61–66 Gy, but not of 45–53 Gy, 54–59 Gy, or at least 67 Gy.
These findings suggest “[t]here may be flexibility in the multimodality treatment planning, including the time to initiate immunotherapy, which may alleviate barriers to immunotherapy treatment in some patients,” conclude the researchers.
“Further study to refine the implications of immunotherapy in clinical stage III NSCLC in a clinical setting is justified.”
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