Reuters Health – 14/09/2021 – The combination of two immune-checkpoint inhibitors (durvalumab and tremelimumab) plus platinum-based chemotherapy significantly improves progression-free survival and overall survival compared with chemotherapy alone in patients with metastatic non-small-cell lung cancer (NSCLC), according to results of the POSEIDON trial.
Lead investigator Dr. Melissa Johnson of the Sarah Cannon Research Institute, in Nashville, Tennessee, reported the results at the World Conference on Lung Cancer (WCLC) 2021, hosted by the International Association for the Study of Lung Cancer (IASLC).
Durvalumab is an anti-PD-L1 agent and tremelimumab is an anti-CTLA-4 agent.
Immunotherapies targeting the PD-1/PD-L1 pathway have “transformed” the treatment of mNSCLC as monotherapy and in combination with chemotherapy, Dr. Johnson said during a press briefing.
“And there is emerging evidence that adding anti-CTLA-4 therapy to anti-PD1/PD-L1 therapy may confer additional clinical and long-term survival benefit in select patient populations,” she noted.
The POSEIDON trial enrolled 1,013 patients with treatment-naive, EGFR/ALK wild-type mNSCLC with random assignment to one of three treatment regimens:
1) Durvalumab (1,500 mg) and chemotherapy every three weeks for four cycles followed by durvalumab (1,500 mg) every four weeks until progression.
2) Durvalumab (1,500 mg) with tremelimumab (75 mg) concurrently with chemotherapy every three weeks for up to four cycles, followed by durvalumab (1,500 mg) every four weeks until progression, with one additional dose of tremelimumab after the fourth dose of chemotherapy.
3) Chemotherapy every three weeks for up to six cycles.
Chemotherapy options (investigator choice) included platinum and pemetrexed for patients with non-squamous histology; platinum and gemcitabine for patients with squamous histology; or carboplatin and nab-paclitaxel for patients with either histology.
Durvalumab plus tremelimumab plus chemotherapy reduced the risk of death by 23% versus chemotherapy alone (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.92), with median overall survival of 14.0 months versus 11.7 months for chemotherapy alone.
Median progression-free survival was 6.2 months with durvalumab plus tremelimumab plus chemotherapy versus 4.8 months with chemotherapy alone (HR 0.72; 95% CI, 0.60 to 0.86).
Durvalumab plus chemotherapy improved PFS by 26% (HR, 0.74; 95% CI, 0.62 to 0.89), with median progression-free survival of 5.5 months versus 4.8 months for chemotherapy alone, but did not significantly improve overall survival.
“With no new safety signals identified, durvalumab plus tremelimumab plus chemotherapy represents a potential new frontline treatment option for metastatic non-small-cell lung cancer,” Dr. Johnson told the briefing.
The POSEIDON trial was sponsored by AstraZeneca.
SOURCE: https://wclc2021.iaslc.org/ 2021 World Conference on Lung Cancer, presented September 9, 2021.
By Megan Brooks
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