Perioperative Tislelizumab Shows Marked Benefit in Both Squamous and Nonsquamous Resectable NSCLC

Neoadjuvant tislelizumab (BGB-A317) plus platinum-based doublet chemotherapy (PtDb) followed by surgery and adjuvant tislelizumab demonstrated consistent benefit over PtDb alone across various patient subgroups, including different PD-L1 expression levels, histologies, and clinical stages, marking a significant advancement in the treatment landscape for patients with resectable non–small cell lung cancer (NSCLC), according to Federico Cappuzzo, MD.

Data from the phase 3 RATIONALE-315 trial (NCT04379635) presented during the February ESMO Virtual Plenary demonstrated that perioperative tislelizumab provided an event-free survival (EFS) benefit vs neoadjuvant placebo plus PtD, with a hazard ratio (HR) of 0.56 (95% CI, 0.40-0.79; P = .0003) at a median follow-up of 22.0 months (range, 0.1-38.4). The median EFS by blinded independent central review was not reached in either arm. Notably, a trend in overall survival (OS) benefit favoring perioperative tislelizumab vs placebo was also observed.

“This is a very important trial that contributes significantly to change the standard of practice in early-stage disease, where now neoadjuvant chemoimmunotherapy can be considered the new standard of care,” said Cappuzzo, who is the director of the Oncology and Hematology Departments at AUSL della Romagna-Ravenna, in Italy.

In an interview with OncLive^®, Cappuzzo expanded on key data from the RATIONALE-315 trial of perioperative tislelizumab in NSCLC; emphasized the trial’s unique focus on squamous histology, a population historically underrepresented in clinical trials; and underscored the potential of perioperative tislelizumab to revolutionize NSCLC treatment paradigms on a global scale.

OncLive: Please provide some background on the RATIONALE-315 trial of perioperative tislelizumab in NSCLC.

Cappuzzo: RATIONALE-315 was a phase 3 randomized trial comparing neoadjuvant chemoimmunotherapy vs standard platinum-based chemotherapy. This is a clinical trial that was designed for patients irrespective of the histology and [those with disease] stages II to IIIA. When we look at the characteristics of patients who were included in this trial, we observe that most patients had squamous histology and all patients from this trial were in Asia.

What key results were seen with this regimen in the study?

In terms of results, the data are impressive, particularly the pathological complete response rate. In other clinical trials with neoadjuvant chemoimmunotherapy, [these rates] range from 18% to 25%. In this trial, it was more than 40%, with a major pathological response [rate] of more than 55%. In terms of the EFS and overall survival, the EFS was significantly in favor of patients receiving the neoadjuvant chemoimmunotherapy. The OS data were also presented. These are preliminary data on OS but clearly there is a trend favoring patients who received neoadjuvant tislelizumab and chemotherapy.

Did the benefit achieved with this regimen differ according to PD-L1 status, disease histology, or clinical stage?

This benefit was present in all subgroups of patients irrespective of the PD-L1 expression, meaning that the benefit was not driven by overexpression of PD-L1. [In fact], the group of patients benefiting more in this trial were those with low levels of PD-L1 expression.

Squamous histology was particularly represented in this clinical trial, but the benefit was present in [those with] squamous as well as nonsquamous histology. Another important message [from this trial] is that the benefit [with this regimen] was present irrespective of [disease] stage; it produced a significant benefit in stage II disease, as well as in the group of patients with stage IIIA disease. This is a very important trial, showing an impressive benefit, particularly in the group of patients with squamous histology, [which is] more represented in this trial.

Why is it significant that perioperative tislelizumab showed a comparable magnitude of benefit in patients with both nonsquamous or squamous histology?

In other clinical trials, patients [with squamous disease] were underrepresented, and in general, the outcomes of these patients were less favorable than the outcomes [of those] with nonsquamous histology. In this trial, we have evidence of benefit even in this group of patients. One of the general concerns [regarding] this neoadjuvant treatment is the [potential] delay of surgery, but no delay in surgery was observed in this study. Also, the toxicity profile was exactly what we expected from chemoimmunotherapy regimen.

We have more clear benefit in [patients with] squamous cell disease, because more than 70% of the trial population were those with squamous histology. Normally, in lung cancer, the percentage of patients with squamous histology is around 25%...We have an additional clinical trial that was conducted in almost all patients with squamous histology and showed a clear benefit in this very difficult-to-treat group of patients.

This is a very important message for clinical practice. In the group of patients with nonsquamous histology, we have the same magnitude of benefit. That is exactly what we expect even with other immunotherapeutic agents.

Reference

Yue D, Wang W, Liu H, et al. VP1-2024: RATIONALE-315: event-free survival (EFS) and overall survival (OS) of neoadjuvant tislelizumab (TIS) plus chemotherapy (CT) with adjuvant TIS in resectable non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35(3):P332-P333. doi:10.1016/j.annonc.2024.01.005