Second-line treatment with sintilimab improved survival compared with docetaxel, in patients with advanced / metastatic squamous non-small cell lung cancer (sqNSCLC) in a phase 3 trial.
Second, Sintilimab improved overall survival (OS) and progression-free survival (SFP) Yuankai Shi, MD, from the Chinese Academy of Medical Sciences and the Beijing Union Medical University in Beijing.
Shi presented these findings, from the ORIENT-3 study, at the 2021 annual meeting of the American Association for Cancer Research: Week 1 (Summary CT041).
ORIENT-3 enrolled and randomized 290 patients with stage IIIB / IIIC or IV sqNSCLC and disease progression during or after the first platinum-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 mean age was 60 years in the sintilimab arm and 61 years in the docetaxel arm. Most patients were male (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 a ECOG performance status of 1 (76% and 77%, respectively). More than half of the patients had a PD-L1 tumor ratio (TPS) score of 1% or higher (57% and 47%, respectively) and 81% of the patients in both arms had stage IV disease.
Results: survival and safety
Patients in the sintilimab arm received an average of 8.0 cycles of therapy (range, 1–45), and those in the docetaxel arm received an average of 2.0 cycles of therapy (range, 1–15).
At a mean 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 (risk ratio, 0.74; Pg = .02489). The advantages of the operating system were generally consistent across all subgroups.
PFS secondary endpoints and objective response rate also favored sintilimab, Shi reported.
The median PFS was 4.30 months in the sintilimab arm and 2.79 months in the docetaxel arm (HR, 0.52; Pg <.00001). The confirmed objective response rates were 25.5% and 2.2%, respectively; the mean 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 with respect to docetaxel, with a lower frequency of adverse events related to grade 3 or higher treatment, with no new safety signs observed,” Shi said.
Treatment-related adverse events (TRAEs) occurred in 84.7% of patients receiving sintilimab and in 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 common in the sintilimab arm than in the docetaxel arm (18.1% vs. 36.2%). Discontinuation rates due to TRAEs were 12.5% and 5.4% in the sintilimab and docetaxel arms, respectively. The TRAEs that caused the death occurred in five patients in the sintilimab arm and one in the docetaxel arm.
Use in the real world
Noting the significant OS and PFS benefits of sintilimab, as well as the superior response rate and duration of response, Shi concluded, “Sintilimab could provide an alternative second-line treatment option for advanced and metastatic sqNSCLC.”
AACR moderator Marina Garassino, MD, of the University of Chicago, commented on the potential utility of sintilimab and tislelizumab, another control point inhibitor that was evaluated in NSCLC in the RATIONALE 303 trial (AACR 2021, Summary CT039). Garassino noted that both drugs have demonstrated superiority to docetaxel as second-line therapy in NSCLC.
Although there have been no side-by-side trials, sintilimab and tislelizumab appear to be very similar to the already approved immune control point inhibitors, which are currently used as first-line treatment.
“This similarity would make them unsuitable for second-line treatment, except in countries where immune control point inhibitors are not yet approved for first-line therapy,” Garassino noted.
When asked to comment on the highest treatment-related mortality rate observed with sintilimab, Garassino said, “We must remember that these drugs were developed in China with a population that may have a profile of effects. “We are very familiar with this kind of drug and we know how to treat its side effects. Similar drugs, but different populations and different trials, so it’s very difficult to judge.”
Garassino speculated that with the “super-expensive” price tags of the new checkpoint inhibitors, it would be welcome to have additional agents who could offer options and reduce prices.
ORIENT-3 was funded by Innovent Biologics and Eli Lilly. Shi unveiled the advice of Innovative Biologics. Garassino revealed relationships with Eli Lilly, AstraZeneca, Novartis and several other companies, not including Innovent Biologics.
This article originally appeared on MDedge.com, which is part of the Medscape professional network.