Limited Course of Tremelimumab, Imfinzi Combination Sustained Overall Survival Improvements in Non-Squamous Non–Small Cell Lung Cancer

Author(s):

An estimated 31.4% of individuals with non-squamous non–small cell lung cancer treated with the combination were alive at 3 years compared to 17.3% for those on chemotherapy alone.

A limited course of tremelimumab, when added to durvalumab (Imfinzi; AstraZeneca), plus 4 cycles of chemotherapy demonstrated a sustained improvement in overall survival (OS) compared to chemotherapy alone in the first-line treatment of individuals with metastatic non–small cell lung cancer (NSCLC), according to the results of a study presented at the European Society of Medical Oncology Congress 2022.

After approximately 4 years of follow-up of the POSEIDON phase 3 trial, additional post-hoc, exploratory analyses continued to show an OS improvement with the combination in individuals with STK11, KEAP1, and KRAS-mutated NSCLC and individuals whose tumors were PD-L1-negative.

"These updated POSEIDON results at nearly 4 years of follow-up show further evidence that the addition of a limited course of tremelimumab to [durvalumab] plus chemotherapy improves outcomes for metastatic [NSCLC] cancer patients, including those with specific tumor mutations where a high unmet need for effective, well tolerated treatments remains," Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said in a statement.

The data show that a course of 5 cycles of tremelimumab added to durvalumab and a platinum-based chemotherapy improved OS by 25% compared to chemotherapy alone. Investigators observed an updated median OS of 14 months for the combination and 11.7 months for chemotherapy alone.

Furthermore, approximately 25% of patients treated with the combination were alive at 3 years compared to 13.6% for those who were treated with chemotherapy alone.

Additionally, a trend of OS improvement continued to be observed in individuals with STK11, KEAP1, and KRAS-mutated metastatic NSCLC when treated with the combination, and reduced the risk of death by 38%, 57%, and 45%, respectively.

The combination also extended sustained OS benefits to individuals with less than 1% PD-L1 tumor cell expression. Consistent with previous POSEIDON data, the OS benefit in the updated results were more pronounced with tremelimumab plus durvalumab and chemotherapy in individuals with non-squamous NSCLC histology.

There was a 32% improvement of OS for the combination compared to chemotherapy alone and an updated median of 17.2 months compared to 13.1 months, respectively. Additionally, an estimated 31.4% of individuals with non-squamous NSCLC treated with the combination were alive at 3 years compared to 17.3% for those on chemotherapy alone.

Investigators also found that the combination was well-tolerated with no new safety signals identified based on serious adverse events (AEs) reported during the approximate 4-year follow-up. Serious AEs of any grade were observed in 27.6% of individuals in the combination arm and 17.7% in the chemotherapy alone arm.

Investigators warned that the interpretations of the data should be viewed with caution due to the small sample sizes. Tremelimumab is under review by global regulatory authorities to be used in the combination as treatment in the first-line of metastatic NSCLC based on these findings.

Reference

Exploratory analysis from POSEIDON phase III trial also showed trends for overall survival benefit with a limited course of tremelimumab added to Imfinzi and chemotherapy in subgroups with high unmet need. News release. AstraZeneca. September 11, 2022. Accessed September 12, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-tremelimumab-with-chemotherapy-demonstrated-sustained-survival-benefit-in-metastatic-non-small-cell-lung-cancer.html