medwireNews: People with resectable stage III non-small-cell lung cancer (NSCLC) could benefit from the addition of the PD-1 inhibitor toripalimab to perioperative chemotherapy, indicate Chinese trial data.
The co-primary endpoints of investigator-assessed event-free survival (EFS) and independently assessed major pathologic response (MPR) were both significantly improved with the use of toripalimab, “while maintaining a manageable safety profile,” report the Neotorch researchers in JAMA.
These findings “support the use of toripalimab in combination with platinum-based chemotherapy as a new treatment option” for this patient population, they add.
The double-blind phase 3 study included 404 patients (median age 62 years, 92% men) with stage III NSCLC lacking EGFR or ALK alterations. The participants were randomly assigned to receive toripalimab 240 mg or placebo every 3 weeks together with platinum-based chemotherapy for three cycles before and one cycle after surgery, followed by maintenance toripalimab at the same dose or placebo for up to 13 cycles.
At a median follow-up of 18.3 months, the median EFS duration was not reached for patients in the toripalimab group and was 15.1 months for those in the placebo group. This equated to a significant hazard ratio (HR) for an event (disease progression leading to the inability to operate, postoperative progression, local or distant recurrence, or death) of 0.40 in favor of the toripalimab combination.
A total of 84.4% of toripalimab-treated patients were alive and event-free at the 1-year mark compared with 57.0% of placebo-treated patients; the respective rates at 2 years were 64.7% and 38.7%.
The MPR rate was significantly higher with toripalimab than placebo, at 48.5% versus 8.4%, and this was also the case for the pathologic complete response rate, at 24.8% versus 1.0%.
Shun Lu (Shanghai Jiao Tong University, China) and co-investigators also found that adding toripalimab to chemotherapy was associated with a significant improvement in disease-free survival, with the median unreached versus 19.3 months with placebo plus chemotherapy.
And there was a trend toward better overall survival in the toripalimab than placebo group – the median durations were unreached and 30.4 months, respectively, and the HR for death was a borderline significant 0.62.
The safety profile of the toripalimab–chemotherapy combination in the current study was consistent with that observed previously, say Lu and colleagues.
Of note, treatment-emergent adverse events (TEAEs) of grade 3 or worse, TEAEs leading to discontinuation, and fatal AEs occurred in a comparable proportion of patients in the toripalimab and placebo study arms, at 63.4% versus 54.0%, 9.4% versus 7.4%, and 3.0% versus 2.0%, respectively.
TEAEs of any grade that were more frequent in the toripalimab than placebo group included cough (34.2 vs 23.3%), increased aspartate aminotransferase levels (31.7 vs 19.8%), decreased appetite (27.7 vs 14.4%), rash (20.3 vs 9.4%), and hypothyroidism (16.8 vs 3.5%).
The researchers also highlight that “the combination treatment did not affect the R0 resection rate or increase the incidence of surgery-related adverse events,” and indeed, more patients in the toripalimab group were able to undergo curative surgery.
The team concludes: “The results from the current study (together with the KEYNOTE-671 study and the AEGEAN trial) establish the critical role of a perioperative checkpoint blocker in patients with resectable NSCLC.”
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