Perioperative Tislelizumab Improves Outcomes in NSCLC

Incorporating perioperative tislelizumab into treatment with neoadjuvant chemotherapy and surgery can improve outcomes in patients with stage II-IIIA non-small cell lung cancer (NSCLC), a phase 3 trial suggests.

Patients who received tislelizumab in combination with neoadjuvant chemotherapy, followed by surgery and adjuvant tislelizumab, had higher response rates and longer event-free survival (EFS) than patients who received neoadjuvant chemotherapy and surgery without tislelizumab.

There was a trend toward improved overall survival (OS) with tislelizumab as well, but the OS data are not yet mature.

These results, from the phase 3 RATIONALE-315 trial (ClinicalTrials.gov identifier: NCT04379635), were presented in an ESMO Virtual Plenary session.

The trial included 453 patients with stage II-IIIA, EGFR/ALK wild-type NSCLC. The patients were randomly assigned to the tislelizumab arm (n=226) or the placebo arm (n=227). Baseline characteristics were well balanced between the arms.

Patients in the tislelizumab arm received 3 to 4 cycles of neoadjuvant tislelizumab (200 mg every 3 weeks) and chemotherapy, followed by surgery and up to 8 cycles of adjuvant tislelizumab (400 mg every 6 weeks). Patients in the placebo arm received neoadjuvant chemotherapy and placebo, surgery, and adjuvant placebo.

Chemotherapy consisted of paclitaxel plus cisplatin or carboplatin for patients with squamous NSCLC. Patients with non-squamous NSCLC received pemetrexed plus cisplatin or carboplatin.

The median follow-up was 22.0 months. In the tislelizumab arm, 211 patients completed neoadjuvant treatment, 190 underwent surgery, and 106 completed adjuvant tislelizumab. In the placebo arm, 210 patients completed neoadjuvant treatment, 173 underwent surgery, and 101 completed adjuvant placebo.

Efficacy and Safety Results  

The major pathologic response rate was 56.2% in the tislelizumab arm and 15.0% in the placebo arm (P <.0001). The pathologic complete response rate was 40.7% and 5.7%, respectively (P <.0001).

The median EFS was not reached in either arm, but there was a significant improvement in EFS with tislelizumab (hazard ratio [HR], 0.56; 95% CI, 0.40-0.79; P =.0003). The 12-month EFS rate was 80.0% in the tislelizumab arm and 68.1% in the placebo arm. The 24-month EFS rate was 68.3% and 51.8%, respectively.

Tislelizumab was associated with improved EFS in patients with squamous and non-squamous NSCLC and in patients with stage II and stage IIIA disease.

The median OS was not reached in either treatment arm, but there was a trend toward improved OS in the tislelizumab arm (HR, 0.62; 95% CI, 0.39-0.98; P =.0193). The 12-month OS rate was 94.5% in the tislelizumab arm and 90.9% in the placebo arm. The 24-month OS rate was 88.6% and 79.4%, respectively.

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 72.1% of patients in the tislelizumab arm and 66.4% of those in the placebo arm. The rate of serious TRAEs was 15.5% and 8.0%, respectively.

The most common grade 3 or higher TRAEs (in the tislelizumab and placebo arms, respectively) were neutrophil count decrease (61.1% and 59.3%) and white blood cell count decrease (16.8% and 14.2%).

There were 4 fatal TRAEs in the tislelizumab arm, including infection, pneumonia, pneumonitis, and immune-mediated lung disease. The 2 fatal TRAEs in the placebo arm were respiratory hemorrhage and cardiac failure.

“These data support the use of perioperative tislelizumab plus neoadjuvant chemo for patients with resectable stage II-IIIA non-small cell lung cancer,” said study presenter Dongsheng Yue, MD, of the Tianjin Medical University Cancer Institute and Hospital in China.

Disclosures: This study was supported by BeiGene Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor