Tremelimumab/Durvalumab Plus Chemotherapy Improves OS in PD-L1–Negative NSCLC

The addition of tremelimumab to durvalumab (Imfinzi) and chemotherapy improved clinical benefit and survival benefit vs. chemotherapy alone in patients with PD-L1–negative metastatic non–small cell lung cancer (mNSCLC), according to results from the phase 3 POSEIDON study (NCT03164616) presented at the 2022 World Lung Cancer Conference.¹

Median overall survival (OS) favored the tremelimumab plus durvalumab and chemotherapy group, and OS benefit was greater in patients who received durvalumab plus chemotherapy in the patient group with PD-L1 tumor cells (TC) of at least 1%, according to lead author Edward B. Garon, MD, MS, professor of medicine, Geffen School of Medicine at the University of California Los Angeles.

The median OS for patients with PD-L1 TC of 1% or greater was 15.6 months (95% CI, 11.6-18.1) with the couplet plus chemotherapy, 14.4 months (95% CI, 11.8-17.5) with durvalumab plus chemotherapy, and 12.6 months (95% CI, 10.4-15.2) in the chemotherapy-alone group. Median OS for patients with PD-L1 less than 1% were 12.7 months (95% CI, 9.9-15.5) for the tremelimumab plus durvalumab and chemotherapy group, 10.9 months (95% CI, 8.1-13.5) for durvalumab plus chemotherapy, and 11.0 months (95% CI, 8.7-12.7) with chemotherapy alone.

Patients with mNSCLC (N = 1013) were randomized 1:1:1 to receive 75 mg of tremelimumab plus 1500 mg of durvalumab plus chemotherapy once every 3 weeks for 4 cycles, 1500 mg of durvalumab plus chemotherapy once every 3 weeks for 4 cycles, or chemotherapy once every 3 weeks up to 6 cycles. End points included OS, progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety in subgroups with PD-L1 status of 1% or greater and less than 1% as well as across different histology types.

The median PFS for patients with PD-L1 (TC) of 1% or greater was 6.2 months (95% CI, 5.0-6.6) with tremelimumab, durvalumab, and chemotherapy, 6.4 months (95% CI, 4.9-6.7) with durvalumab and chemotherapy, and 4.9 months (95% CI, 4.9-6.0) with chemotherapy alone. The median PFS for patients with PD-L1 TC less than 1% was 6.1 months (95% CI, 4.6-6.5), 4.6 months (95% CI, 4.0-5.0), and 4.7 months (95% CI, 4.6-6.2), respectively.

Patients with non-squamous disease with PD-L1 TC of 1% or greater had median OS of 22.1 months (95% CI, 15.9-27.8) with the doublet and chemotherapy, 17.1 months (95% CI, 13.3-23.9) with durvalumab plus chemotherapy, and 13.5 months (95% CI, 10.6-18.8) with chemotherapy alone. Patients with non-squamous disease with PD-L1 TC of less than 1% had a median OS of 13.4 months (95% CI, 9.8-18.7), 11.7 months (95% CI, 7.5-17.0), and 12.3 months (95% CI, 9.3-14.1), respectively.

Patients with squamous disease and PD-L1 TC of 1% or greater had a median OS of 9.8 months (95% CI, 7.6-12.5) with tremelimumab plus durvalumab plus chemotherapy, 12.3 months (95% CI, 9.5-15.7) with durvalumab plus chemotherapy, and 10.6 months (95% CI, 9,0-15.2) with chemotherapy alone. These same patients but with PD-L1 TC less than 1% had median OS of 12.7 months (95% CI, 7.7-14.1), 9.8 months (95% CI, 7.4-13.5), and 8.8 months (95% CI, 4.8-11.8), respectively.

In patients with PD-L1 TC expression 1% or greater, those who received the triplet combination had an ORR of 40.0%. Patients who received the doublet combination had an ORR of 49.1% and those who received chemotherapy alone had an ORR of 27.6%.

The median DOR heavily favored the doublet plus chemotherapy group with PD-L1 TC of 1% or greater. The median DOR in this group was 16.4 months (95% CI, 7.2-nonestimable), and the median DOR for durvalumab plus chemotherapy was 7.2 months (95% CI, 5.6-12.7), and 5.1 months (95% CI, 4.2-5.4) with chemotherapy alone. Median DOR for patients with PD-L1 TC less than 1% were 7.8 months (95% CI, 5.1-12.5), 6.7 months (95% CI, 3.8-9.0), and 5.5 months (95% CI, 3.7-12.7), respectively.

Treatment-related adverse events (AEs) and grade 3 and 4 AEs were similar among the treatment types within their respective patient subgroups and consistent across the whole population.

These results suggest adding tremelimumab to durvalumab and chemotherapy as a treatment option for patients with low or PD-L1 negative mNSCLC.

Reference

Garon EB, Cho BC, Luft A, et al. Durvalumab (d) ± tremelimumab (t) + chemotherapy (ct) in 1l metastatic nsclc: outcomes by tumour pd-l1 expression in POSEIDON. E-Poster presented at the 2022 World Lung Cancer Conference; August 6-9, 2022; Vienna, Austria. Accessed August 4, 2022. https://bit.ly/3oUDJ8B