medwireNews: Treatment-naïve patients with locally advanced or metastatic squamous non-small-cell lung cancer (NSCLC) derive a significant progression-free survival (PFS) benefit from the addition of the novel PD-1 inhibitor tislelizumab to chemotherapy, demonstrates a Chinese phase 3 trial.
The tislelizumab combination almost halved the risk for progression or death relative to chemotherapy alone as well as improving response rates, report Jie Wang (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing) and team in JAMA Oncology.
“The results of this trial suggest that tislelizumab in combination with chemotherapy is an appropriate first-line treatment option” for this patient population, they add.
In the RATIONALE 307 study, 360 patients with stage IIIB (33.9%) or IV (66.1%) disease that was not amenable to curative surgery or radiotherapy were randomly assigned to receive intravenous tislelizumab 200 mg every 3 weeks alongside paclitaxel 175 mg/m2 on day 1 or nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 plus carboplatin AUC 5 on day 1, or the paclitaxel–carboplatin combination alone.
Over a median follow-up of 8.6 months, the primary endpoint of PFS by independent review was significantly prolonged with the addition of tislelizumab to chemotherapy, at a median of 7.6 months each in the tislelizumab–paclitaxel and tislelizumab–nab-paclitaxel combination arms versus 5.5 months in the chemotherapy alone group. The stratified hazard ratios for progression or death were 0.524 and 0.478, respectively, favoring the triplet regimens.
“These benefits were observed regardless of PD-L1 expression and in most prespecified subgroup analyses,” highlight Wang and colleagues.
The addition of tislelizumab also achieved higher objective response rates, at 73% with the tislelizumab–paclitaxel combination and 75% with the tislelizumab–nab-paclitaxel combination versus 50% with chemotherapy alone. The median duration of response was also longer in the tislelizumab groups, at 8.2 and 8.6 months, respectively, versus 4.2 months.
Reporting on the safety profile, Wang et al note that the combination of tislelizumab and chemotherapy was “generally well tolerated,” and add that “[a]dverse events reported across both tislelizumab-containing arms were consistent with established safety profiles of PD-1/L1 inhibitors and chemotherapy.”
Grade 3 or worse treatment-related adverse events (TRAEs) occurred in 85.8% of patients given the tislelizumab–paclitaxel combination, 83.9% of those given the tislelizumab–nab-paclitaxel combination, and 80.3% of those given chemotherapy alone. The researchers note, however, that these TRAEs “were mostly hematologic in nature and consistent with known chemotherapy AEs.”
They add that the rate of discontinuation of any treatment component due to treatment-emergent AEs was “low,” at 12.5%, 29.7%, and 15.4%, respectively. The team speculates that the increased rate in the nab-paclitaxel group “may be because of more frequent administration and safety assessments with nab-paclitaxel (once weekly) compared with paclitaxel (every 3 weeks).”
In all, there were six deaths due to TRAEs, with one, two, and three in the tislelizumab–paclitaxel, tislelizumab–nab-paclitaxel, and chemotherapy alone groups, respectively, but none were considered solely related to tislelizumab.
The author of an accompanying commentary describes the trial as “well-conducted,” but notes that several questions remain unanswered, such as the relevance of the results for routine clinical practice, “for which the standard of care for patients with stage IIIB disease is curative intent combined modality therapy.”
He also questions “the value of another immune checkpoint inhibitor in this space, especially when the results at best mirror those of a preexisting standard and the evidence was generated from somewhat less rigorous clinical trial methods.”
Nonetheless, Raymond Osarogiagbon (Baptist Cancer Center, Memphis, Tennessee, USA) concludes that “[c]onfirmation of these results in a more diverse population of patients with squamous cell lung cancer should be quickly sought and lead to acceptance of tislelizumab as a viable alternative immunotherapy choice, which can expand access to the global community of patients with advanced non–small-cell lung cancer.”
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JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.0366
JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.0262