Real-world pneumonitis rates with pembrolizumab–chemotherapy exceed clinical trial data
medwireNews: A Japanese real-world study has found higher rates of pneumonitis with first-line pembrolizumab plus chemotherapy among patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) than previously reported in clinical trials.
Most cases of pneumonitis occurred within the first 90 days of patients initiating treatment, and so the researchers propose that “patients should undergo careful surveillance during the initial 90-day period following the commencement of the combination therapy.”
The study included 299 patients with treatment-naïve, stage III–IV or recurrent, nonsquamous NSCLC who received the combination of pembrolizumab, pemetrexed, and platinum-based chemotherapy at one of 36 Japanese hospitals between December 2018 and June 2019.
During a median follow-up of 5.5 months, 12.4% of patients developed pneumonitis of any grade and 3.3% of patients had grade 3 or higher pneumonitis, making it the most common severe nonhematologic treatment-related adverse event (AE) among the study participants.
By contrast, in the KEYNOTE-189 trial of the combination in this patient population, “the frequency of all-grade and severe pneumonitis was 4.4% and 2.7%, which are lower than those in our study, and these reported rates are despite the longer follow-up period than that of our study,” say the researchers in the European Journal of Cancer.
“These results strongly suggest that the incidence of pneumonitis following the combination therapy was higher in real-world settings than in clinical trials,” they continue.
Of note, just over half (56.8%) of the 37 patients with any-grade pneumonitis developed the AE within 90 days of initiating treatment, as did all but one of the 10 patients with grade 3 or worse pneumonitis. The median time to pneumonitis onset was 2.6 months and the majority (73.0%) of patients with pneumonitis discontinued treatment.
The researchers also highlight that developing pneumonitis “worsens the survival outcome” of patients in this setting. After adjusting for immortal time bias and relevant clinical factors, pneumonitis was significantly associated with worse overall survival and progression-free survival, with respective hazard ratios of 3.03 and 1.99.
Satoru Miura (Niigata Cancer Center Hospital, Japan) and co-investigators stress “the importance of clinicians carefully observing pneumonitis signs,” and conclude: “Further investigation is necessary to improve the safety of this combination therapy.”
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