Imfinzi plus Tremelimumab with Chemotherapy Demonstrates Significant Improvement in Progression-Free and Overall Survival in First-Line Stage IV NSCLC

September 09, 2021 /BioonBIOON/ --AstraZeneca(AstraZeneca) recently announced positive results from the Phase 3 POSEIDON study at the 2021 World Conference on Lung Cancer (WCLC 2021). The study evaluatedAnti-PD-L1 therapy Imfinzi (Yingfeifan; generic name: durvalumab) in combination with anti-CTLA-4 therapy tremelimumab and chemotherapy, versus chemotherapy alone, as first-line treatment for stage IV (metastatic) non-small cell lung cancer (NSCLC)Efficacy and safety in patients.

The results showed,Compared with patients receiving chemotherapy, those treated with Imfinzi + tremelimumab + chemotherapy demonstrated statistically and clinically significant improvements in overall survival (OS) and progression-free survival (PFS) (28% improvement in PFS and 23% improvement in OS). These results indicate that adding a short course of tremelimumab to the Imfinzi plus chemotherapy regimen improves patient outcomes without increasing treatment discontinuation.

AstraZenecaTumorSusan Galbraith, Executive Vice President of Research & Development, said: "The POSEIDON trial data further demonstrate the benefits of Imfinzi for patients, serving as a key validation of our strategy to explore new combination development approaches. For patients who have previously received chemotherapy, adding a short course of tremelimumab to Imfinzi reduced the risk of disease progression or death by 28% compared with chemotherapy alone. The results also indicate that the significant survival benefit in the first-line treatment of patients with metastatic non-small cell lung cancer was achieved without compromising tolerability. We look forward to discussing these data with regulatory authorities."

POSEIDON was a randomized, open-label, multicenter, global phase 3 clinical trial evaluating the efficacy and safety of Imfinzi + platinum-based chemotherapy, Imfinzi + tremelimumab + chemotherapy, and chemotherapy alone as first-line treatment for patients with metastatic NSCLC. The study enrolled patients with non-squamous and squamous disease across the full range of PD-L1 expression levels, and excluded patients harboring EGFR or ALK gene mutations.

The results show:Over a 16-week period, patients treated with Imfinzi plus chemotherapy and a short course of tremelimumab for 5 cycles had a 23% reduction in the risk of death compared with a range of chemotherapy regimens.(HR = 0.77; 95% CI: 0.65–0.92; p = 0.00304). The median OS for patients in the combination therapy group was 14.0 months, compared with 11.7 months in the chemotherapy group. At 2 years, the estimated survival rate was 33% in the combination therapy group versus 22% in the chemotherapy group.

In addition,Compared with chemotherapy, treatment with Imfinzi plus chemotherapy plus tremelimumab also reduced the risk of disease progression or death by 28%.(HR = 0.72; 95% CI: 0.60–0.86; p = 0.00031). The median PFS for patients in the combination therapy group was 6.2 months, compared with 4.8 months in the chemotherapy group. The safety profile of the Imfinzi + chemotherapy + tremelimumab regimen was comparable to that of the Imfinzi + chemotherapy regimen, with no increase in treatment discontinuations.

The POSEIDON study also evaluated the efficacy of Imfinzi plus chemotherapy,Results showed: Compared with chemotherapy, patients treated with Imfinzi + chemotherapy demonstrated a statistically significant improvement in PFS (HR=0.74; 95% CI: 0.62-0.89; p=0.00093). The positive OS trend observed with Imfinzi + chemotherapy did not reach statistical significance.

In this study, the safety profile of each Imfinzi combination regimen was consistent with the known safety profiles of the individual drugs, and no new safety signals were identified.

Lung cancer is the leading cause of cancer death in both men and women, accounting for approximately one-fifth of all cancer deaths. Lung cancer is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for approximately 80–85% of cases. Within NSCLC, patients are classified as having squamous cell carcinoma (approximately 25–30%) or non-squamous cell carcinoma (approximately 70–75%). Stage IV lung cancer is the most advanced stage of the disease and is commonly referred to as metastatic disease. At the time of diagnosis, the majority of patients already have cancer that has spread beyond the lungs. For patients with metastatic disease, the prognosis is very poor, with a 5-year survival rate of only 10% following diagnosis.

Imfinzi is a human monoclonal antibody that selectively binds to programmed death-ligand 1 (PD-L1), blocking the interaction of PD-L1 with PD-1 and CD80, counteringTumorimmune evasion strategies and relieve the suppression of immune responses.

Based on the results of the Phase III PACIFIC study,Imfinzi is the only approved immunotherapy for curative-intent treatment in patients with unresectable stage III non-small cell lung cancer (NSCLC) following chemoradiotherapy, and has now become the global standard of care.. Furthermore, based on the results of the Phase 3 CASPIAN study,Imfinzi has also been approved in multiple countries worldwide for the treatment of extensive-stage small cell lung cancer (ES-SCLC).

Currently, AstraZeneca is conducting multiple registration trials focused on evaluating Imfinzi for the treatment of early-stage lung cancer, including in potentially curable settings (Phase III trials such as PACIFIC-2, -4, -5, MERMAID-1, -2, AEGEAN, ADJUVANT BR.31, and ADRIATIC, etc.). Additionally, the company is conducting two Phase II platform trials, COAST (in unresectable Stage III) and NeoCOAST (in the neoadjuvant early-stage setting), to test novel combination therapies with Imfinzi. (Bioon.com)

Original Source:Imfinzi and tremelimumab with chemotherapy improved progression-free survival by 28% and overall survival by 23% in 1st-line Stage IV non-small cell lung cancer vs. chemotherapy