In a detailed study, researchers have shed light on the complexities of measuring the effectiveness of cancer treatments through progression-free survival (PFS) and overall survival (OS) endpoints. These endpoints, crucial in assessing therapeutic efficacy in oncology drug development, are frequently compromised by various factors, including protocol design, intercurrent events, and inconsistent data collection. The study, led by Daiichi Sankyo Company Ltd., highlights the importance of adopting a prospective ICH E9(R1) estimand framework to mitigate these risks and ensure the robustness of survival endpoints.

Key Takeaways:

• The quality and interpretability of PFS and OS endpoints in oncology clinical trials are frequently challenged by methodological and operational complexities.
• Discontinuation of study treatment, initiation of subsequent anticancer therapy, lost to follow-up, and withdrawal of consent can introduce significant bias, limiting the robustness of survival endpoints.
• Adopting a prospective ICH E9(R1) estimand framework can help mitigate risks associated with data collection, analysis methodology, and interpretability.
• Integration of ICH E9(R1) offers a harmonized strategy that is important for the design and conduct of randomized late phase oncology clinical trials.
• The research concludes that the quality and interpretability of PFS and OS endpoints according to the ICH E9(R1) framework are critical components in designing and conducting robust oncology clinical trials.
• The study provides practical recommendations for designing and conducting robust oncology clinical trials, underscoring the importance of adopting a prospective ICH E9(R1) estimand framework.
• The research emphasizes the need for a harmonized strategy in evaluating PFS and OS endpoints, aligning with the FDA guidance on oncology endpoints and the EMA guideline on anticancer medicinal product evaluation.

Statistics:

• Progression-free survival (PFS) and overall survival (OS) endpoints are critical in assessing therapeutic efficacy in oncology drug development.
• Methodological and operational complexities can obscure the true treatment effect, introducing significant bias in survival endpoints.
• A prospective ICH E9(R1) estimand framework can help mitigate risks associated with data collection, analysis methodology, and interpretability in oncology clinical trials.
• The research highlights the importance of adopting a harmonized strategy in evaluating PFS and OS endpoints, as outlined by the FDA guidance on oncology endpoints and the EMA guideline on anticancer medicinal product evaluation.
• The study provides practical recommendations for designing and conducting robust oncology clinical trials, underscoring the need for a prospective ICH E9(R1) estimand framework.

Sources:

• Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival In Oncology Clinical Trials. Therapeutic Innovation & Regulatory Science, 2025.
• Daiichi Sankyo Company Ltd. (2025). Study Findings on Drugs and Therapies Are Outlined in Reports from Daiichi Sankyo Company Ltd. (Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival In Oncology Clinical Trials). Clinical Trials Week. October 20, 2025; p 140.