Addition of Tremelimumab to Durvalumab Regimen Induces Greater Survival Outcomes in PD-L1–Negative NSCLC
The phase 3 POSEIDON trial showed superior overall survival in patients with PD-L1–negative metastatic non–small cell lung cancer who were given durvalumab and chemotherapy plus tremelimumab.
Results from the phase 3 POSEIDON trial (NCT03164616) that were presented at the 2022 World Conference on Lung Cancer demonstrated that better survival and clinical benefit was possible when patients with PD-L1–negative metastatic non–small cell lung cancer (mNSCLC) were treated with tremelimumab plus durvalumab (Imfinzi) and chemotherapy vs durvalumab and chemotherapy alone.
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 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 value in 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.
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.
