The addition of tislelizumab to chemotherapy was found to prolong progression-free survival (PFS) compared with chemotherapy alone in patients who had advanced non-small cell lung cancer (NSCLC) with squamous histology, according to the results of a study published in JAMA Oncology.

Tislelizumab is an anti-PD-1 antibody that was designed to reduce antibody-dependent phagocytosis, which may be a mechanism of anti-PD-1 therapy resistance. Prior phase 2 studies suggested that the combination of tislelizumab plus chemotherapy may have efficacy in squamous NSCLC.

The open-label, phase 3 RATIONALE307 trial ( Identifier: NCT03594747) randomly assigned 355 patients with squamous NSCLC to receive tislelizumab plus paclitaxel and carboplatin (arm A), tislelizumab plus nab-paclitaxel and carboplatin (arm B), or paclitaxel and carboplatin (arm C). The primary endpoint was PFS, and secondary endpoints included overall survival, objective response rate, duration of response, and safety.

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At baseline, the median age was 62, 91.7% of patients were men, and 83.6% were current or former smokers. Patients had stage IV (66.1%) or stage IIIB (33.9%) disease, and PD-L1 expression was less than 1 among 40%, 1% to 49% among 25.3%, and at least 50% among 34.7%.

During a median follow-up of 8.6 months, tislelizumab plus chemotherapy was found to prolong PFS with a median of 7.6 months in both combination arms compared with 5.5 months for chemotherapy (hazard ratio for arm A, 0.524; 95% CI, 0.370-0.742; P <.001 and for arm B, 0.478; 95% CI, 0.336-0.679; P <.001).

The objective response rate was also higher at 72.5% and 74.8% in both tislelizumab arms (combined with paclitaxel and carboplatin or nab-paclitaxel and carboplatin, respectively) compared with 49.6% for chemotherapy alone.

Response and PFS were not associated with PD-L1 expression levels.

Treatment-emergent adverse events (TEAEs) that resulted in treatment discontinuation occurred among 12.5% and 29.7% of patients in the tislelizumab plus paclitaxel or nab-paclitaxel arms, respectively, and carboplatin arms compared with 15.4% in the chemotherapy arm. The most common grade 3 or higher TEAEs were hematologic.

The authors concluded that “The results of this trial suggest that tislelizumab in combination with chemotherapy is an appropriate first-line treatment option in patients with advanced squamous NSCLC.”

Disclosure: Several study authors declared affiliations with academic and medical institutions. Please see the original reference for a full list of authors’ disclosures.


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. A phase 3 randomized clinical trial. JAMA Oncol. Published online April 1, 2021. doi:10.1001/jamaoncol.2021.0366