Tislelizumab Maintains OS Benefit vs Docetaxel in Previously Treated NSCLC


Results from the phase 3 RATIONALE-303 trial presented at 2022 WCLC showed an overall survival benefit when patients with non–small cell lung cancer were treated with second- or third-line tislelizumab compared with docetaxel.

Tislelizumab (BGB-A317) given in the second- or third-line setting resulted in improved overall survival (OS) compared with docetaxel for patients with non–small cell lung cancer (NSCLC), according to results of the phase 3 RATIONALE-303 trial (NCT03358875) that were presented at the 2022 World Conference on Lung Cancer.1

Median follow-up for the tislelizumab arm was 16.0 months and 10.7 months for the docetaxel arm. The median OS for patients in the intention-to-treat (ITT) population administered tislelizumab (n = 535) was 16.9 months (95% CI, 15.2-19.1) compared with 11.9 months (95% CI, 9.6-13.5) for patients who received docetaxel (n = 270; HR, 0.66; 95% CI, 0.56-0.79; P < .0001). The 12- and 24-month OS rates for tislelizumab were 62.1% and 36.8%, respectively, and 49.7% and 23.7%, respectively, for docetaxel.

Patients with PD-L1 expression of at least 25% of tumor cells (PD-L1 positive) treated with tislelizumab (n = 227) had a median OS of 19.3 months (95% CI, 16.5-22.6) vs 11.5 months (95% CI, 8.2-13.5) with docetaxel (n = 116; HR 0.53; 95% CI, 0.40-0.70; P < .0001). The 12- and 24-month OS rates were 67.4% and 42.3%, respectively, for patients in the tislelizumab arm compared with 47.8% and 22.3%, respectively, for patients in the docetaxel arm.

The previously reported interim analysis of RATIONALE-303 showed that tislelizumab significantly prolonged OS vs docetaxel leading to the agent’s approval in China in January 2022 for patients with advanced NSCLC who experienced disease progression after chemotherapy.2

RATIONALE-303 enrolled adult patients aged at least 18 years with histologically confirmed, locally advanced, or metastatic squamous or nonsquamous NSCLC. Patients were required to provide fresh or archival tumor tissue samples for PD-L1 evaluation, have an ECOG performance status of 0 or 1, have acceptable hematologic and end-organ function, and have a life expectancy of more than 12 weeks.3

Key exclusion criteria included prior treatment with docetaxel or a PD-1, PD-L1, or CTLA-4 inhibitor; the presence of EGFR or ALK aberrations; a history of severe hypersensitivity reactions to other monoclonal antibodies; or a history of interstitial lung disease.

The trial randomized 805 patients 2:1 to receive 200 mg of intravenous (IV) tislelizumab every 3 weeks or 75 mg/m2 of IV docetaxel every 3 weeks.

OS in the PD-L1–positive and ITT populations served as the trial’s coprimary end points. Secondary end points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), health-related quality of life, and safety.

Study authors noted that baseline demographics and disease characteristics were representative of the target population, and they were well balanced between both arms, including for PD-L1 expression and histology.1

Additional data showed that patients in the ITT population treated with tislelizumab experienced a median PFS of 4.2 months (95% CI, 3.9-5.5) compared with 2.6 months (95% CI, 2.2-3.8) for patients given docetaxel (HR, 0.63; 95% CI, 0.53-0.75). Among PD-L1–positive patients, the median PFS with tislelizumab was 6.5 months (95% CI, 6.2-8.3) vs 2.4 months (95% CI, 2.1-4.1) with docetaxel (HR, 0.37; 95% CI, 0.28-0.49).1

The ORR in the ITT population was 22.6% and 7.0% for the tislelizumab and docetaxel arms, respectively. In PD-L1–positive patients, the ORR was 37.4% and 6.9% for tislelizumab and docetaxel, respectively. The median DOR in the ITT population was 13.5 months (95% CI, 8.5-19.6) for tislelizumab compared with 6.0 months (95% CI, 2.1-7.2) for docetaxel. The DOR in the PD-L1–positive population was 11.9 months (95% CI, 8.3-19.6) for tislelizumab and 4.2 months (95% CI, 0.6-6.1) for docetaxel.

A post-hoc biomarker analysis showed that patients with NOTCH1-4 mutations treated with tislelizumab (n = 26) had a median OS of 24.7 months (95% CI, 14.2–not applicable [NA]) compared with 7.7 months (95% CI, 3.3-14.3) in patients with NOTCH1-4 mutations given docetaxel (n = 15; HR, 0.22; 95% CI, 0.10-0.49; 1-sided stratified log-rank P = .0002). For patients who did not harbor NOTCH1-4 mutations, the median OS for those treated with tislelizumab (n = 218) was 15.7 months (95% CI, 13.9-17.9) compared with 12.9 months (95% CI, 10.4-14.9) for those administered docetaxel (n = 101; HR, 0.75; 95% CI, 0.57-0.99; P = .0390).

Patients with NOTCH1-4 mutations who received tislelizumab had a median PFS of 14.1 months (95% CI, 6.2-NA) compared with 2.6 months (95% CI, 2.0-4.1) for those who received docetaxel (HR, 0.17; 0.08-0.37; P < .0001). In patients without NOTCH1-4 mutations, tislelizumab elicited a median PFS of 4.1 months (95% CI, 2.2-6.2) vs 3.3 months (95% CI, 2.1-4.1) for docetaxel (HR, 0.72; 95% CI, 0.55-0.95; P = .0197).

Though tumor mutational burden was associated with a PFS benefit for patients treated with tislelizumab vs docetaxel, it was not correlated with an OS benefit, except at the highest cutoff of at least 14 mutations per megabase.

As of the July 25, 2021, data cutoff, 66 patients in the tislelizumab arm and 3 patients in the docetaxel arm were still on treatment. In the tislelizumab group, reasons for discontinuation included radiographic disease progression (n = 229), loss of clinical benefit (n = 121), adverse effects (AEs; n = 61), patient withdrawal (n = 19), clinical progressive disease (n = 23), physician decision (n = 9), concurrent antineoplastic therapy (n = 1), lost to follow-up (n = 2), and other (n = 3).

Reasons for discontinuation in the docetaxel group included radiographic disease progression (n = 168), AEs (n = 32), patient withdrawal (n = 28), clinical progressive disease (n = 15), physician decision (n = 10), concurrent antineoplastic therapy (n = 1), and protocol deviation (n = 1).

No new safety signals were reported in the final analysis. Any-grade treatment-emergent AEs (TEAEs) occurred in 96.8% of patients given tislelizumab compared with 98.4% of patients given docetaxel. The rates of grade 3 or higher TEAEs were 42.1% and 74.8%, respectively.

Common TEAES of any grade included increased ALT (20.6% and 15.1% in the tislelizumab and docetaxel arms, respectively), increased AST (19.5% and 12.4%), decreased weight (16.1% and 11.6%), cough (21.3% and 15.5%), anemia (29.2% and 44.6%), and decreased appetite (16.5% and 24.0%).


  1. Zhou C, Huang D, Fan Y, et al. Tislelizumab versus docetaxel in previously treated advanced non-small cell lung cancer: final analysis of RATIONALE-303. Presented at: International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract EP08.01-014.
  2. China NMPA approves tislelizumab as second- or third-line treatment for patients with locally advanced or metastatic non-small cell lung cancer. News release. Beigene. January 6, 2022. Accessed August 5, 2022. https://bit.ly/3P7bNJf

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