First-Line Tislelizumab Plus Chemotherapy May Be ‘Viable’ For Advanced Squamous NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Initial results from the phase III open-label RATIONALE 307 trial suggest that patients with advanced squamous non-small-cell lung cancer (NSCLC) may derive significant benefit from use of the PD-1 inhibitor tislelizumab alongside first-line chemotherapy. 

After a median 8.6 months of follow-up, the independent review committee (IRC)-assessed progression-free survival (PFS) was a median 7.6 months for Chinese stage IIIB/IV patients who were randomly assigned to receive tislelizumab 200 mg on day 1 of a 21-day cycle alongside paclitaxel plus carboplatin (n=120) and also for those instead given the PD-1 inhibitor with nab-paclitaxel plus carboplatin (n=119). 

These durations were significantly longer than the median IRC-PFS of 5.5 months for the 121 patients who received paclitaxel plus carboplatin alone, report Jie Wang, from the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, and co-workers in JAMA Oncology. 

Both the tislelizumab treatment arms also had significantly higher IRC-assessed objective response rates than the chemotherapy only arm (72.5 and 74.8% vs 49.6%, respectively) and remained in response for longer (median 8.2, 8.6 and 4.2 months, respectively). 

Jie Wang and co-workers note that PFS and response to tislelizumab did not differ by PD-L1 expression, nor disease stage, prompting them to suggest that the “the positive PFS benefits observed in patients with stage IIIB disease suggest a potential new treatment option for this patient population.” 

However, the author of an invited commentary, Raymond Osarogiagbon, from the Baptist Cancer Center in Memphis, Tennessee, USA, questions the relevance of the findings to the standard of care for stage IIIB patients who would usually be considered candidates for chemotherapy with curative intent, radiation and consolidative durvalumab “rather than immunotherapy platinum triplet therapy, which must still be regarded as palliative intent therapy.” 

Treatment-emergent adverse events (TEAEs) led to discontinuation in 12.5% of patients given tislelizumab with paclitaxel plus carboplatin and 15.4% of those given only paclitaxel plus carboplatin, but 29.7% of patients who received tislelizumab with nab-paclitaxel plus carboplatin. 

“This increased rate may be because of more frequent administration and safety assessments with nab-paclitaxel (once weekly) compared with paclitaxel (every 3 weeks)”, comment Jie Wang and co-authors. 

Nevertheless, the team says that tislelizumab plus chemotherapy “was generally well tolerated” and toxicity was “consistent with established safety profiles of PD-1/L1 inhibitors and chemotherapy”, with the most common grade 3 and more severe TEAEs mirroring the reductions in neutrophils and white blood cells and neutropenia found in the chemotherapy arm. 

Raymond Osarogiagbon writes that “[t]his well-conducted randomized clinical trial reveals tislelizumab as a viable new first-line treatment option for patients with advanced/metastatic squamous cell [NSCLC] irrespective of [PD-L1] expression levels.” 

But he notes that in the absence of a predictive biomarker, the trial may need to be repeated in “a more diverse population” as there are potential differences in cancer biology and drug kinetics between Chinese and non-Chinese individuals. 

Finally, he cautions that the RATIONALE 307’s overall survival data have yet to mature. “With 46% of doublet therapy patients crossing over to receive tislelizumab on progression, time will tell if the trial achieves the overall survival secondary end point”, Raymond Osarogiagbon concludes. 

References  

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; Advance online publication 1 April 2021. doi:10.1001/jamaoncol.2021.0366  

Osarogiagbon RU. Tislelizumab–A promising new option for enhancing chemotherapy benefit in treatment for advanced squamous cell lung cancer. JAMA Oncol; Advance online publication 1 April 2021. doi:10.1001/jamaoncol.2021.0262