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 (ClinicalTrials.gov 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.
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