Tislelizumab Plus Chemotherapy Improved Efficacy and Maintained Safety to Treat Squamous NSCLC

Combination therapy with tislelizumab/chemotherapy improved progression-free survival and the overall response rate for patients with squamous non–small cell lung cancer when compared with chemotherapy alone.

Tislelizumab plus chemotherapy led to significantly prolonged independent review committee (IRC)–assessed progression-free survival (PFS) and overall response rate (ORRs), while maintaining a tolerable safety profile for patients with squamous non–small cell lung cancer (sq-NSCLC), according to data published in JAMA Oncology.

The combination significantly improved outcomes compared with chemotherapy alone regardless of PD-L1 expression in the patient population in the phase 3 RATIONALE 307 trial (NCT03594747).

“The addition of tislelizumab to standard chemotherapy demonstrated a significant reduction to the risk of progression or death for patients with advanced sq-NSCLC,” wrote the investigators. “This represents an additional treatment option as first-line treatment for patients with sq-NSCLC.”

A total of 355 patients with sq-NSCLC were randomized 1:1:1 to receive either tislelizumab plus paclitaxel and carboplatin (arm A); tislelizumab plus nab-paclitaxel (Abraxane) and carboplatin (arm B); or paclitaxel and carboplatin (arm C). The population included in the research had a median age of 62 years (range, 34-74) and was majority male (91.7%). Median follow-up time was 8.6 months (95% CI, 8.1-9.0 months).

The IRC-assessed PFS for both arms A 7.6 months compared with 5.5 months for arm C. Hazard ratios for the comparison with arm C were significant for both arm A (HR, 0.524; 95% CI, 0.370-0.742; P < .001) and arm C (HR, 0.478; 95% CI, 0.336-0.679; P < .001).

More, both an increased IRC-assessed ORR and longer IRC-assessed duration of response were observed in arm A (72.5% ORR; 8.2 months) and arm B (74.8% ORR; 8.6 months) compared with arm C (49.6% ORR; 4.2 months).

The safety profile remained tolerable, with treatment discontinuations because of adverse events found in 12.5% of patients in arm A, 29.7% of patients in arm B, and 15.4% of patients in arm C. The most common grade 3 or worse adverse event was a decrease in neutrophil levels across all 3 arms. While there were 6 treatment-related adverse events that led to deaths, none of the deaths were attributed solely to tislelizumab.

“To our knowledge, RATIONALE 307 is one of the first phase 3 trials of a PD-1 inhibitor in combination with chemotherapy in sq-NSCLC to include patients with stage IIIB disease who were not amenable to curative surgery or chemoradiotherapy,” wrote the investigators. “Subgroup analyses of PFS demonstrated that tislelizumab plus chemotherapy provided benefits compared with chemotherapy alone, regardless of disease stage.”

The primary end point of the trial was IRC-assessed PFS. Overall survival, investigator-assessed PFS, IRC-assessed ORR, and IRC-assessed duration of response were all among the key secondary end points of the research.

A main strength of the data according to the researchers was the IRC evaluation of the primary end point. The team wrote that, “evaluation of the primary end point was strengthened by the use of an IRC, which were consistent with that of the investigators, suggesting that the PFS end point was not confounded by the knowledge of treatment assignment.”

Investigator bias due to the open-label design of the trial was described as a potential limitation of the research. To counter the potential for bias, the research team implemented a number of measures to ensure the validity of the data.


Wang J, Lu S, Yu X, et al. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non–Small-Cell Lung Cancer. JAMA Oncol. Published April 1, 2021. doi:10.1001/jamaoncol.2021.0366