medwireNews: Adding toripalimab to standard first-line chemotherapy significantly improves the outcomes of people with extensive-stage small-cell lung cancer (ES-SCLC), indicate results from the Chinese EXTENTORCH trial.
The trial met both its primary endpoints of improved progression-free survival (PFS) and overall survival (OS), “while maintaining a tolerable safety profile,” report Ying Cheng (Jilin Cancer Hospital, Changchun, China) and co-researchers in JAMA Oncology.
The team continues: “The findings of this trial support this combination regimen as a first-line treatment option for patients with ES-SCLC.”
In a related commentary, Saiama Waqar and fellow authors (all from Washington University in St Louis, Missouri, USA) say that “[t]hese results, however, have limited therapeutic implications since chemoimmunotherapy had already been established as the standard of care several months prior to the start of EXTENTORCH trial accrual.”
They add: “Furthermore, with the differences in baseline patient characteristics compared to studies performed in a predominantly Western population, the use of toripalimab beyond Chinese population may require confirmation in a global study.”
Outlining the background to the study, Cheng et al explain that “[p]revious studies of PD-L1 inhibitors combined with chemotherapy have shown significant survival benefits in patients with ES-SCLC,” but PD-1 inhibitors “have shown mixed results.”
In the double-blind phase 3 trial, they investigated toripalimab, “a novel immunoglobulin G4 PD-1 blocking antibody, [which] has a unique FG loop binding site on PD-1 receptor and higher binding affinity than pembrolizumab and nivolumab.”
The participants – all of whom had previously untreated ES-SCLC – were randomly assigned to receive either intravenous toripalimab 240 mg or placebo every 3 weeks, alongside etoposide plus either cisplatin or carboplatin, for up to four to six cycles. This was followed by maintenance treatment with toripalimab or placebo for up to 2 years unless patients developed disease progression or intolerable toxicity.
At a median follow-up of 13.7 months, the risk for progression or death was reduced by a significant 33% with the addition of toripalimab rather than placebo to chemotherapy. The respective median PFS times were 5.8 and 5.6 months, and the PFS rates at 6 months and 1 year were 47.1% versus 36.3% and 18.1% versus 4.9%, respectively.
Add-on toripalimab was also associated with a significant 20% reduction in the risk for death, with a median OS duration of 14.6 months versus 13.3 months with placebo. The 1-year OS rates were 63.1% and 54.9%, respectively, and the 2-year rates were 25.9% and 19.5%.
“Notably, the median OS of the placebo group in the current trial is longer than that of the most pivotal trials of immune checkpoint inhibitors plus chemotherapy in patients with ES-SCLC,” say the investigators, speculating that one possible reason could be that more patients in the placebo than toripalimab group received subsequent systemic therapy.
Nevertheless, “[s]ensitivity analyses demonstrated that the survival benefit still favored toripalimab plus chemotherapy after adjusting for subsequent therapies,” they continue.
With regard to the safety, the incidence of grade 3 or worse treatment-emergent adverse events (TEAEs) was nearly identical between the toripalimab and placebo arms, at rates of 89.6% and 89.4%, respectively.
TEAEs led to discontinuation of any study drug in 12.6% of patients in the toripalimab group and 7.9% of those in the placebo group, with fatal TEAEs occurring in a respective 5.4% and 3.2% of participants.
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JAMA Oncol 2024; doi:10.1001/jamaoncol.2024.5019
JAMA Oncol 2024; doi:10.1001/jamaoncol.2024.4958
