J Clin Oncol: Efficacy of devarumab± tramimumab and chemotherapy in first-line treatment of metastatic non-small cell lung cancer

Immunotherapies targeting programmed cell death-1 (PD-1) and its ligand (PD-L1), either as monotherapy or in combination with existing chemotherapy, have transformed first-line treatment
for metastatic non-small cell lung cancer (mNSCLC).

The open-label phase 3 POSEIDON study evaluated the efficacy and safety
of tremelimumab in combination with durvalumab and chemotherapy (T+D+CT) and devarumab in combination with chemotherapy (D+CT) compared with chemotherapy alone (CT) for the first-line treatment of metastatic NSCLC.

In this trial, 1013 patients with EGFR/ALK wild-type metastatic NSCLC were randomized (1:1:1) to receive trimezumab (75 mg) + devarumab (1500 mg) and platinum-based chemotherapy (up to 4 courses), followed by maintenance (1 time/4 weeks) with devarumab; or devarumab + chemotherapy (up to 4 courses), followed by devarumab maintenance; or chemotherapy (up to 6 courses), no maintenance therapy or maintenance therapy
with pemetrexed.
The primary endpoints were progression-free survival (PFS) and overall survival (OS)
in the D+CT group compared to the CT group.
Key secondary endpoints were PFS and OS
in the T+D+CT group compared to the CT group.

CT group vs D+CT group PFS and OS

The results showed that PFS was significantly longer in the D+CT group compared with the CT group (median PFS: 5.
5 vs 4.
8 months; HR 0.
74, p=0.
0009), OS showed no statistically significant improvement (median OS: 13.
3 vs 11.
7 months; HR 0.
86, p=0.
0758; 24-month OS rate: 29.
6% vs 22.
1%)
.
PFS in the T+D+CT group compared with the CT group (median PFS: 6.
2 vs 4.
8 months; HR 0.
72, p=0.
0003) and OS (median OS: 14.
0 vs 11.
7 months; HR 0.
77, p=0.
0030; 24-month OS rate: 32.
9% vs 22.
1%) were significantly extended
.

T+D+CT group vs PFS and OS of CT group

The incidence of treatment-related grade 3/4 adverse events in the T+D+CT, D+CT and CT groups was 51.
8%, 44.
6% and 44.
4%, respectively; Treatment was discontinued due to
treatment-related adverse events in 15.
5%, 14.
1%, and 9.
9% of patients, respectively.

In summary, compared with chemotherapy alone, devarumab combined with chemotherapy significantly prolonged progression-free survival in patients with metastatic non-small cell lung cancer.
Tramemezumab combined with devarumab and chemotherapy significantly prolongs overall and progression-free survival in patients with metastatic non-small cell lung cancer without significant additional tolerability burden, representing a potential new first-line option for
mNSCLC.

Original source:

Melissa L.
Johnson, et al.
Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study.
Journal of Clinical Oncology.
November 3, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
00975