Durvalumab with or without tremelimumab in combination with chemotherapy in first-line metastatic non-small-cell lung cancer

An updated analysis from the phase 3 POSEIDON study recently published on ESMO Open shows that a first line treatment with tremelimumab plus durvalumab and chemotherapy consistently improved clinical outcomes in patients with metastatic non-small-cell lung cancer (NSCLC) in both blood tumor mutational burden high or low subgroups and in both high and low tissue tumor mutational burden subgroups.

In the POSEIDON study, after a median follow-up of more than 5 years, first line tremelimumab plus durvalumab and chemotherapy showed durable long-term overall survival benefit versus chemotherapy alone in metastatic NSCLC. Tumor mutational burden (TMB), defined as the number of somatic mutations present in DNA derived from blood (bTMB) or tumor tissue (tTMB), has potential as a predictive biomarker for immunotherapy treatment benefit, in particular for combined anti-PD-L1 plus anti-CTLA-4 therapy independent of PD-L1 expression. Thus, authors analyzed outcomes of POSEIDON patient subgroups defined by a range of bTMB and tTMB values. Results showed an overall survival and progression free survival benefit for tremelimumab plus durvalumab and chemotherapy in both bTMB-high and bTMB-low subgroups and both tTMB-high and tTMB-low subgroups at all cut-offs, with a magnitude of benefit greater in TMB-high compared with TMB-low subgroups. As authors conclude, «In patients with metastatic NSCLC, first-line treatment with a limited course of tremelimumab plus durvalumab (until progression) and four cycles of chemotherapy consistently improved clinical outcomes versus chemotherapy alone. Benefit appeared greater in the TMB-high compared with TMB-low subgroups; the addition of anti-CTLA-4 to anti-PD-L1 and chemotherapy seemed to increase the magnitude of this difference. However, in view of the limited benefit, TMB testing is not warranted in this setting».