Sintilimab improved both overall survival (OS) and progression-free survival (PFS), according to Yuankai Shi, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.
Dr. Shi presented these findings, from the ORIENT-3 study, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT041).
ORIENT-3 enrolled and randomized 290 patients with stage IIIB/IIIC or IV sqNSCLC and disease progression during or after first-line platimum-based chemotherapy. They were randomized 1:1 to receive sintilimab at 200 mg or docetaxel at 75 mg/m2intravenously every 3 weeks until disease progression or intolerable toxicity.
The median age was 60 years in the sintilimab arm and 61 years in the docetaxel arm. A majority of patients were men (94% in the sintilimab arm and 90% in the docetaxel arm), most were current or former smokers (90% and 80%, respectively), and more than three-quarters had an ECOG performance status of 1 (76% and 77%, respectively). More than half of patients had a PD-L1 tumor proportion score (TPS) of 1% or greater (57% and 47%, respectively), and 81% of patients in both arms had stage IV disease.
Results: Survival and safety
Patients in the sintilimab arm received a median of 8.0 cycles of therapy (range, 1-45), and those in the docetaxel arm received a median of 2.0 cycles of therapy (range, 1-15).
At a median follow-up of 23.56 months, the median OS was significantly longer in the sintilimab arm than in the docetaxel arm – 11.79 months and 8.25 months, respectively (hazard ratio, 0.74; P = .02489). OS benefits were generally consistent across subgroups.
The secondary endpoints of PFS and objective response rate also favored sintilimab, Dr. Shi reported.
The median PFS was 4.30 months in the sintilimab arm and 2.79 months in the docetaxel arm (HR, 0.52; P < .00001). Confirmed objective response rates were 25.5% and 2.2%, respectively; the median duration of response was 12.45 months and 4.14 months, respectively; and disease control rates were 65.5% and 37.8%, respectively.
“Sintilimab had a favorable safety profile over docetaxel, with a lower frequency of grade 3 or higher treatment-related adverse events, with no new safety signals observed,” Dr. Shi said.
Treatment-related adverse events (TRAEs) occurred in 84.7% of patients receiving sintilimab and 83.1% of those receiving docetaxel. Hypothyroidism was the most common TRAE in the sintilimab arm (18.1%), and alopecia was the most common TRAE in the docetaxel arm (34.6%).
Grade 3 or higher TRAEs were less frequent in the sintilimab arm than in the docetaxel arm (18.1% vs. 36.2%). Rates of discontinuation because of TRAEs were 12.5% and 5.4% in the sintilimab and docetaxel arms, respectively. TRAEs leading to death occurred in five patients in the sintilimab arm and one in the docetaxel arm.
Use in the real world
Noting sintilimab’s significant OS and PFS benefits as well as superior response rate and duration of response, Dr. Shi concluded, “Sintilimab might provide an alternative second-line treatment option for advanced and metastatic sqNSCLC.”