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Tislelizumab continued to demonstrate an improved clinical benefit compared with docetaxel in both Asian and non-Asian patients with previously treated advanced non–small cell lung cancer.
Tislelizumab (BGB-A317) continued to demonstrate an improved clinical benefit compared with docetaxel in both Asian and non-Asian patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a final subgroup analysis of the phase 3 RATIONALE-303 trial (NCT03358875) presented during the 2022 ESMO Congress.1
At a data cutoff of July 15, 2021, an improved overall survival (OS) trend was noted with the anti–PD-1 monoclonal antibody (n = 424) compared with the chemotherapy (n = 219) in the Asian population. The median OS was 17.8 months (95% CI, 15.4-20.6) vs 12.2 months (95% CI, 9.4-13.8), respectively (HR, 0.65; 95% CI, 0.54-0.79). In the non-Asian population, the median OS with tislelizumab (n = 111) was 14.9 months (95% CI, 11.8-17.5) vs 11.9 months (95% CI, 7.0-15.0) with docetaxel (n = 51; HR, 0.73; 95% CI, 0.48-1.11).
Treatment with tislelizumab (n = 424) also prolonged progression-free survival (PFS) vs docetaxel (n = 219) in the Asian population, with a median PFS of 4.1 months (95% CI, 3.3-4.3) and 2.4 months (95% CI, 2.1-3.6), respectively (HR, 0.62; 95% CI, 0.51-0.75). In the non-Asian population, the median PFS with tislelizumab and docetaxel was 6.3 months (95% CI, 4.2-8.3) and 4.1 months (95% CI, 2.2-5.8), respectively (HR, 0.67; 95% CI, 0.45-1.00).
Moreover, in the Asian subgroup, tislelizumab elicited an objective response rate (ORR) of 21.5% vs 5.9% with docetaxel. The median duration of response (DOR) was 13.8 months (95% CI, 9.0-21.8) in the investigative arm vs 4.2 months (95% CI, 2.1-7.2) in the control arm. In the non-Asian subgroup, the ORRs achieved with tislelizumab and docetaxel were 27.0% and 11.8%, respectively; the median DORs were 10.3 months (95% CI, 6.2-19.9) and 6.1 months (95% CI, 2.1-12.5), respectively.
“In the RATIONALE-303 study, tislelizumab improved OS and consistently demonstrated favorable efficacy benefits compared with docetaxel, including PFS, ORR, and DOR, in both Asian and non-Asian patients with previously treated advanced NSCLC,” Caicun Zhou, MD, PhD, of the Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China, and colleagues, wrote in a poster on the data.
Tislelizumab was specifically engineered to minimize Fcγ receptor binding on macrophages.
RATIONALE-303 enrolled adult patients with histologically confirmed, locally advanced or metastatic squamous or nonsquamous NSCLC that progressed during or after treatment with at least 1 platinum-containing regimen. Patients could not have received more than 2 previous lines of systemic chemotherapy.
Study participants were randomly assigned 2:1 to receive intravenous (IV) tislelizumab at 200 mg or IV docetaxel at 75 mg/m2 every 3 weeks.
The coprimary end points of the trial were OS in the intention-to-treat (ITT) population and in the population of patients with a PD-L1 expression of at least 25% on tumor cells. Key secondary end points comprised investigator-assessed PFS, ORR, DOR, and safety.
At the time of the interim analysis of the trial, which had a data cutoff date of August 10, 2020, tislelizumab significantly improved OS over docetaxel in the ITT population.2 These findings supported the Chinese approval of the agent in patients with advanced NSCLC who had disease progression after chemotherapy.3 At the final analysis, which had a data cutoff of July 15, 2021, the monoclonal antibody continued to improve OS over the chemotherapy in this population.4
As part of a poster presentation during the 2022 ESMO Congress, investigators shared data from the final analysis of the Asian and non-Asian subgroups examined on the trial.
A total of 643 Asian patients and 162 non-Asian patients underwent randomization between November 2017 and April 2020. At the time of the final analysis, the median follow-up for tislelizumab was 17.2 months vs 10.7 months for docetaxel in the Asian subset; in the non-Asian subset, this was 14.3 months and 10.4 months, respectively.
Notably, sites in China started the study approximately 13.5 months prior to sites outside of China.
The baseline characteristics were noted to be generally well balanced between the treatment arms in both subgroups.
Regarding safety, fewer grade 3 or higher treatment-emergent adverse effects (TEAEs) were experienced by Asian patients in the tislelizumab arm vs the docetaxel arm at 41.1% vs 75.2%; serious TEAEs occurred in 35.7% and 31.4% of patients, respectively. In the non-Asian population, grade 3 or higher TEAEs occurred in 45.9% of those who received tislelizumab and 72.9% of those who received docetaxel; 29.7% and 37.5% of patients, respectively, experienced serious TEAEs.
The most common grade 3 or higher TEAEs to occur in at least 25% of Asian patients in the tislelizumab and docetaxel arms, respectively, were anemia (4.0% vs 7.1%), decreased appetite (1.2% vs 1.0%), dyspnea (1.4% vs 1.9%), nausea (0% vs 0.5%), decreased white blood cell count (0.2% vs 21.9%), decreased neutrophil count (0.7% vs 32.4%), leukopenia (0.2% vs 17.1%), fatigue (0% vs 2.9%), neutropenia (0.5% vs 24.8%), and alopecia (0% vs 0.5%).
In the non-Asian patients, the most frequent grade 3 or higher TEAEs experienced by those who received tislelizumab and docetaxel, respectively, included anemia (0.9% vs 6.3%), decreased appetite (0% vs 2.1%), dyspnea (4.5% vs 6.3%), decreased white blood cell count (0% vs 2.1%), decreased neutrophil count (0% vs 6.3%), leukopenia (0% vs 10.4%), fatigue (2.7% vs 4.2%), neutropenia (0.9% vs 41.7%), and alopecia (0% vs 2.1%).
In the Asian subgroup, TEAEs resulted in treatment discontinuation in 10.6% of those who received tislelizumab and 12.4% of those who were given docetaxel; these rates were 17.1% and 16.7% of non-Asian subgroups, respectively.