31May

Frontline durvalumab and tremelimumab combo misses overal survival endpoint in metastatic NSCLC

CCTG BR.34: A randomized trial of durvalumab and tremelimumab +/- platinum-based chemotherapy in patients with metastatic (Stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC).


Abstract No : 9502

Abstract Type : Oral Abstract Session

Indication : Non-Small Cell Lung Cancer

Intervention : Durvalumab and tremelimumab +/- platinum-based chemotherapy

Company : Canadian Cancer Society Research Institute, Pharmaceutical/Biotech Company

Technology : Monoclonal antibody


Results:

At a median follow up of 16.6 months, no significant difference in OS was seen between the two treatment arms, with a median OS of 16.6 months with DT+CT v. 14.1 months with DT, (estimated HR 0.88, 90% CI 0.67-1.16). PFS was significantly improved in the DT+CT arm (stratified HR 0.67, 95% CI 0.52-0.88; medians 7.7 v. 3.2 months). ORR was higher in the DT+CT arm, 28% v. 14%, (odds ratio 2.1, p=0.001). Preplanned subgroup analysis demonstrated no significant differences in treatment outcomes by plasma TMB (,20 v. $20 mut/Mb, Guardant OMNI), age, sex, or smoking status. There was a trend to improved OS with DT+CT in the subgroup with PD-L1 TPS$50%, (HR 0.64, 95% CI 0.40-1.04, p=0.07). Plasma TMB,20 mut/Mb was associated with shorter survival in both treatment groups (HR 1.99, 95% 1.3-3.1). Toxicity was greater in the DT+CT arm, with grade$3 adverse events in 82% v. 70%, (p=0.02), most commonly dyspnea, nausea and cough. The incidence of immune-related adverse events was similar between arms (colitis 11%, pneumonitis 6%, endocrinopathy 21%). Grade 5 events occurred in 2.7%, (5 with DT+CT, 3 with DT).


Conclusion:

The combination of durvalumab (Imfinzi) and tremelimumab did not improve overall survival (OS) compared with standard platinum-based chemotherapy in previously untreated NSCLC patients in phase III NEPTUNE trial. Although company is also evaluating fronline role of durvalumab or durvalumab and tremelimumab in combination with platinum-based chemotherapy in POSEIDON study


Commentary:

Frontline durvalumab and tremelimumab combo misses overal survival endpoint in metastatic NSCLC.


Refer to Non Small Cell Lung Cancer Market report for detailed Insights.