medwireNews: Treatment-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) derive a significant progression-free survival (PFS) survival with the addition of the PD-1 inhibitor sintilimab to chemotherapy, indicates the ORIENT-11 trial.
Other outcomes were also improved with the PD-1 inhibitor versus placebo, including a “nominally significant improvement” in overall survival (OS), and the combination had a “manageable safety profile,” with “no new safety signals,” said presenting author Li Zhang (Sun Yat-sen University Cancer Center, Guangzhou, China).
He reported these data at the IASLC’s World Conference on Lung Cancer Virtual Presidential Symposium 2020.
The double-blind phase 3 study included 397 previously untreated patients with stage IIIB–IV disease lacking EGFR or ALK alterations. Participants were randomly assigned to receive four cycles of sintilimab 200 mg or placebo together with pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC5 every 3 weeks, followed by sintilimab or placebo alongside pemetrexed at the same doses for up to 2 years. Crossover was permitted for the placebo group.
At a median follow-up of 8.9 months, median PFS was 8.9 months for the sintilimab arm and 5.0 months for the placebo arm, a significant difference giving a hazard ratio (HR) for progression or death of 0.48 in favor of the PD-1 inhibitor.
The PFS benefit afforded by sintilimab was maintained across most subgroups, the exceptions being women, patients with brain metastases at baseline, and those with a PD-L1 tumor proportion score of less than 1%.
The OS data were not mature at the time of analysis, with the median unreached in both study arms. But the 6-month OS rate was better for sintilimab- than placebo-treated patients, at 89.6% versus 80.4%, and equated to a significant HR for death of 0.61.
Patients in the sintilimab group also had a higher objective response rate (51.9 vs 29.8%) and disease control rate (86.8 vs 75.6%) than those in the placebo group, and the median duration of response was longer (unreached vs 5.5 months).
With regard to the safety profile, the incidence of grade 3–5 adverse events (AEs), serious AEs, and grade 3–5 immune-related AEs was comparable between the sintilimab and placebo arms, at 61.7% versus 58.8%, 28.2% versus 29.8%, and 5.6% versus 6.1%, respectively.
In all, 6.0% of sintilimab-treated participants discontinued any component of the treatment regimen due to AEs, as did 8.4% of the controls. The corresponding rates of AE-related mortality were 2.3% and 6.9%.
Discussant Misako Nagasaka (Karmanos Cancer Institute, Detroit, Michigan, USA) noted that the ORIENT-11 results are similar to those from other immunotherapy–chemotherapy studies in this setting, and importantly provide information on outcomes in East Asian participants.
She described the PFS benefit of sintilimab as “certainly encouraging,” but cautioned that longer follow-up is required to demonstrate whether this will translate into a significant OS improvement.
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