Consolidation pembrolizumab promising in locally advanced NSCLC
medwireNews: Patients undergoing chemoradiotherapy for unresectable stage III non-small-cell lung cancer (NSCLC) could benefit from consolidation treatment with the PD-1 inhibitor pembrolizumab, suggest phase 2 study results.
The investigators note that the placebo-controlled PACIFIC trial of durvalumab in the same setting, previously reported by medwireNews, demonstrated significant gains in overall survival (OS) and other endpoints with the anti-PD-L1 agent.
“Our trial also demonstrates that pembrolizumab substantially improves outcomes in this patient population and further solidifies the strategy of consolidation PD-1/PD-L1 inhibition as the new standard of care,” write Greg Durm (Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, USA) and colleagues.
The trial included 92 stage IIIA/B patients who had not progressed after concurrent chemotherapy with cisplatin plus etoposide or pemetrexed or carboplatin plus paclitaxel and radiotherapy at a dose of 59.4–66.6 Gy.
At a median follow-up of 32.2 months, the median time to metastatic disease or death (TMDD) was 30.7 months following consolidation therapy with pembrolizumab 200 mg every 3 weeks for up to 12 months. This was significantly longer than the TMDD of 12.0 months for the historical estimate of chemoradiotherapy alone, and meant the trial met its primary endpoint.
The estimated 12-, 18-, 24-, and 36-month TMDD rates were 77.6%, 61.8%, 55.3%, and 49.9%, respectively.
The median OS and progression-free survival (PFS) durations were 35.8 months and 18.7 months, respectively, which “appear to be substantially improved above historical estimates as well,” say Durm and colleagues in Cancer.
The researchers did not identify any variables that were significantly associated with TMDD, PFS, or OS, but outcomes were numerically better for participants who initiated pembrolizumab within 6–8 weeks of finishing chemoradiation relative to those who started within 4–6 weeks.
This finding suggests there is “no detriment from waiting up to 8 weeks before initiating consolidation pembrolizumab to allow for sufficient time for recovery from toxicities of chemoradiation,” they comment.
The study authors say that consolidation treatment with pembrolizumab was well tolerated, with low rates of treatment- and immune-related adverse events of grade 3 or worse. They acknowledge, however, that 43.5% of patients were unable to complete the full year of pembrolizumab, primarily due to disease progression (25.0%) and toxicity (19.6%).
In total, 16 (17.2%) patients developed symptomatic pneumonitis, “an adverse event of high interest,” within a median 8.4 weeks of receiving pembrolizumab, which is “not demonstrably more than what is expected with chemoradiation alone,” say Durm and colleagues. Four patients had grade 3 pneumonitis and one patient each had a grade 4 and 5 event. There was just one additional instance of a high-grade immune-related toxicity, namely grade 4 colitis.
Durm and co-researchers conclude that while consolidation pembrolizumab “signifies a major advance in the treatment of stage III NSCLC, efforts are underway to build off this success.”
They continue: “The optimal timing of PD-1 or PD-L1 inhibitors in the treatment of patients with stage III NSCLC remains an open question.”
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