Sintilimab shows potential as second-line treatment option for squamous NSCLC

The anti-PD-1 monoclonal antibody sintilimab outperformed docetaxel as second-line treatment for advanced and metastatic squamous non-small-cell lung cancer (NSCLC), according to the results of the phase III ORIENT-3 trial presented at AACR 2021.

“Lung cancer is a leading cause of cancer death globally, of which NSCLC accounts for 80–85 percent,” said principal investigator Professor Yuankai Shi from the Chinese Academy of Medical Sciences, Beijing, China, in a press release. “In the past few decades, drug development [for NSCLC] has mainly focused on [the nonsquamous type], while drug development of squamous NSCLC has been slower due to its unique epidemiological, histopathological, and molecular characteristics.”

“Patients with advanced squamous NSCLC have very limited second-line treatment options after failure of platinum-based doublet chemotherapy … In China specifically, the approved options for second-line immunotherapy to treat squamous NSCLC are even more limited,” added Shi.

“[Our findings showed] superior overall survival (OS) and progression-free survival (PFS) benefit [with sintilimab] compared with docetaxel,” said Shi.

After a median follow-up of 23.56 months, the study met its prespecified primary endpoint, given the significantly improved OS with sintilimab compared with docetaxel (median, 11.79 vs 8.25 months; hazard ratio [HR], 0.74, 95 percent confidence interval [CI], 0.56–0.96; p=0.02489). [AACR 2021, abstract CT041]

PFS was also significantly superior in the sintilimab vs the docetaxel arm (median, 4.30 vs 2.79 months; HR, 0.52, 95 percent CI, 0.39–0.68; p<0.00001).

Confirmed objective response rate (ORR) also favoured sintilimab over docetaxel (25.5 percent vs 2.2 percent).

The rates of treatment-related adverse events (TRAEs) were similar between the sintilimab and the docetaxel arms (84.7 percent vs 83.1 percent), the most common being hypothyroidism (18.1 percent) and alopecia (34.6 percent). Grade ≥3 TRAEs were fewer in the sintilimab vs the docetaxel arm (18.1 percent vs 36.2 percent). In terms of death however, there were five reportedly related to sintilimab and one with docetaxel.

Shi and colleagues evaluated 290 participants with stage IIIB/IIIC or IV (ineligible for radical chemoradiotherapy) squamous NSCLC with disease progression during or after first-line platinum-based chemotherapy. They were randomized 1:1 to receive either sintilimab 200 mg or docetaxel 75 mg/m² IV Q3W. Treatment was administered until the emergence of radiographic disease progression, unacceptable toxicities, or other conditions necessitating treatment withdrawal.

“[Taken together, our findings showed that] sintilimab significantly improved OS for second-line treatment of squamous NSCLC, which is of great clinical value,” said Shi. “We hope that the positive results of ORIENT-3 can help more patients with squamous NSCLC.”