Durvalumab–tremelimumab plus chemo ‘a potential new first-line option’ for metastatic NSCLC
medwireNews: The addition of durvalumab plus tremelimumab to chemotherapy significantly improves the outcomes of people with untreated metastatic non-small-cell lung cancer (NSCLC), shows the POSEIDON trial.
Presenting the findings at the IASLC 2021 World Conference on Lung Cancer, Melissa Johnson (Sarah Cannon Research Institute, Nashville, Tennessee, USA) highlighted that patients who received the triplet experienced “statistically significant and clinically meaningful improvements” in both progression-free survival (PFS) and overall survival (OS) versus chemotherapy alone.
“Therefore, durvalumab plus tremelimumab plus chemotherapy represents a potential new front-line treatment option for metastatic non-small-cell lung cancer,” she said.
In the phase 3 trial, 1013 individuals with treatment-naïve, stage IV, nonsquamous or squamous NSCLC lacking EGFR or ALK alterations were randomly assigned to receive one of the following regimens:
- four cycles of durvalumab 1500 mg plus platinum-based chemotherapy every 3 weeks followed by durvalumab maintenance every 4 weeks;
- four cycles of durvalumab 1500 mg plus tremelimumab 75 mg alongside platinum-based chemotherapy every 3 weeks followed by durvalumab maintenance every 4 weeks plus one extra dose of tremelimumab at week 16; or
- platinum-based chemotherapy alone.
After a median follow-up of 10.3 months, the co-primary endpoint of PFS in the durvalumab plus chemotherapy group was significantly better than that in the chemotherapy alone group, at a median of 5.5 versus 4.8 months, and a hazard ratio (HR) for progression or death of 0.74 in favor of the combination.
There was also a trend toward improvement in the other primary endpoint of OS, which was assessed after a median follow-up of 34.9 months, at a median of 13.3 months for the combination and 11.7 months for chemotherapy alone, but this did not reach statistical significance, reported Johnson.
Nevertheless, the positive result for the PFS endpoint allowed the analysis of the key secondary endpoints of PFS and OS for the triplet regimen versus chemotherapy alone, she continued.
The addition of durvalumab plus tremelimumab to chemotherapy significantly boosted both PFS and OS relative to chemotherapy, at medians of 6.2 versus 4.8 months and 14.0 versus 11.7 months, respectively, and corresponding HRs of 0.72 and 0.77.
Johnson noted that the benefit offered by the triplet over chemotherapy alone was especially pronounced among patients with nonsquamous disease, such that in this subgroup the HR for progression or death was 0.66, while the HR for death was 0.70.
She said that “the safety profile was similar to previous reports of immunotherapy plus chemotherapy, with no new safety signals identified.”
Treatment-related adverse events (TRAEs) of grade 3 or 4 occurred in 44.6% of patients receiving durvalumab plus chemotherapy, 51.8% of those receiving durvalumab and tremelimumab plus chemotherapy, and 44.4% of those receiving chemotherapy alone.
The rates of discontinuation due to TRAEs in the three groups were 14.1%, 15.5%, and 9.9%, respectively, with TRAE-related deaths in 2.1%, 3.3%, and 2.4%.
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