First-Line Treatment of Metastatic NSCLC with Durvalumab with or without Tremelimumab in Combination with Chemotherapy: AE Management in the POSEIDON Trial

In the phase 3 POSEIDON study of first-line treatment of metastatic non–small-cell lung cancer (mNSCLC), the addition of the anti–CTLA-4 inhibitor tremelimumab to durvalumab and chemotherapy showed statistically significant improvements in progression-free survival and overall survival compared with chemotherapy alone.¹ In addition, no new safety signals were identified, and treatment discontinuations due to treatment-related adverse events (TRAEs) were similar for both arms: tremelimumab plus durvalumab and chemotherapy (arm A) and durvalumab plus chemotherapy (arm B). Recently, Cho and colleagues presented the adverse events (AEs) observed in the POSEIDON trials and discussed their management strategies.²

The POSEIDON study was a randomized trial that included 1013 patients with EGFR/ALK wild-type mNSCLC who were randomized 1:1:1 to receive first-line tremelimumab plus durvalumab and chemotherapy (arm A, 330 patients), durvalumab plus chemotherapy (arm B, 334 patients), or chemotherapy alone (arm C, 333 patients).²

Hematologic AEs were the most common grade 3/4 TRAEs, including anemia, which was observed in 17%, 15%, and 20%, and neutropenia, which was observed in 16%, 13%, and 12% of patients in arms A, B, and C, respectively. Standard management approaches were used, including administering colony-stimulating factors and blood transfusions.

All-grade immune-related AEs (irAEs) occurred in 34%, 19%, and 5% of patients in arm A, B, and C, respectively. The addition of tremelimumab to durvalumab resulted in a higher incidence of diarrhea/colitis, dermatitis/rash, and endocrinopathies. Grade 3/4 irAEs occurred in 10%, 7%, and 2% of patients in arm A, B, and C, respectively, and serious irAEs occurred in 10%, 6%, and 1%, respectively. The incidence of irAEs that led to discontinuation was higher in arm A than in arms B and C (6%, 4%, and 0.6%, respectively). Similarly, irAEs that led to death were higher in arm A (0.6%, 0.3%, and 0%). However, most irAEs were low-grade and manageable with systemic corticosteroids or endocrine therapy.

In summary, the safety profile of all combination regimens was manageable and consistent with AEs of the individual therapies. The most common grade 3/4 TRAEs were those observed with chemotherapy treatments. More irAEs occurred with the tremelimumab plus durvalumab combination than with durvalumab alone.

References

1. Johnson M, Cho BC, Luft A, et al. Durvalumab ± tremelimumab + chemotherapy as first-line treatment for mNSCLC: results from the phase 3 POSEIDON study. Presented at: Virtual 2021 World Conference on Lung Cancer (WCLC); September 8-14, 2021. Abstract PL02.01.
2. Cho BC, Reinmuth N, Luft A, et al. Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in first-line (1L) metastatic (m) NSCLC: AE management in POSEIDON. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2021; Chicago, IL. Abstract 9035.