Beyond Overall Survival: Advancing the Understanding and Use of Surrogate Endpoints in Oncology
Author(s)
Medha Sasane, PhD1, Ines Bouajila, MSc (HEOR)2, Krupa Paranjpe, Pharm.D3, Céline Fernandez, MD4;
1Sanofi, Oncology HEOR Global Head, Austin, TX, USA, 2Sanofi (at the time this study was conducted), Cambridge, MA, USA, 3Sanofi, Bridgewater, NJ, USA, 4Sanofi, Paris, France
1Sanofi, Oncology HEOR Global Head, Austin, TX, USA, 2Sanofi (at the time this study was conducted), Cambridge, MA, USA, 3Sanofi, Bridgewater, NJ, USA, 4Sanofi, Paris, France
Presentation Documents
OBJECTIVES: The increasing use of non-overall survival (OS) endpoints in oncology trials suggests a shift towards earlier and broader treatment measures. Treatments with novel mechanisms of action requiring lengthy follow-ups for OS have led to increased read-out of surrogate endpoints as primary or co-primary endpoints in several trials. Although regulators are open to considering non-OS early endpoints, payers may remain uncertain about their reimbursement value. We present a review of emerging novel non-OS endpoints relevant to patients with solid tumors/hematological malignancies.
METHODS: A targeted literature review was conducted using Embase (Jan 2019-Feb 2024), hand search of conference records (2022-2023) and grey literature to identify relevant studies evaluating non-OS endpoints. The outcomes of selected studies were summarized qualitatively.
RESULTS: Non-OS endpoints in the identified studies (n=80), including in non-small cell lung cancer and multiple myeloma (MM), and can be categorized as progression-based (progression-free survival, event-free survival, time-to-progression) or response-based (overall response rate, minimal residual disease [MRD], pathological complete response) outcomes. Many of these endpoints are included as additional measures of efficacy in trials and have demonstrated their relevance in clinical practice. The hurdle from reimbursement standpoint is higher; requiring, robust validation studies linking early outcomes to OS. In 2024, the FDA oncologic drug advisory committee (ODAC) supported use of MRD for accelerated approval of MM treatment based on a meta-analysis that used patient-level data to establish MRD as an early endpoint in MM patients1. Translation of this early endpoint in clinical practice and reimbursement decisions remains to be seen.
CONCLUSIONS: Broadening the acceptance of non-OS endpoints by regulators and payers requires. continued actions across the healthcare continuum. This includes establishing patient relevance (via patient-value outcomes such as QoL and daily functioning), translation of clinical trials to the real world, clear reimbursement planning parameters, and stakeholder commitment to ensure timely access to innovative therapies.
METHODS: A targeted literature review was conducted using Embase (Jan 2019-Feb 2024), hand search of conference records (2022-2023) and grey literature to identify relevant studies evaluating non-OS endpoints. The outcomes of selected studies were summarized qualitatively.
RESULTS: Non-OS endpoints in the identified studies (n=80), including in non-small cell lung cancer and multiple myeloma (MM), and can be categorized as progression-based (progression-free survival, event-free survival, time-to-progression) or response-based (overall response rate, minimal residual disease [MRD], pathological complete response) outcomes. Many of these endpoints are included as additional measures of efficacy in trials and have demonstrated their relevance in clinical practice. The hurdle from reimbursement standpoint is higher; requiring, robust validation studies linking early outcomes to OS. In 2024, the FDA oncologic drug advisory committee (ODAC) supported use of MRD for accelerated approval of MM treatment based on a meta-analysis that used patient-level data to establish MRD as an early endpoint in MM patients1. Translation of this early endpoint in clinical practice and reimbursement decisions remains to be seen.
CONCLUSIONS: Broadening the acceptance of non-OS endpoints by regulators and payers requires. continued actions across the healthcare continuum. This includes establishing patient relevance (via patient-value outcomes such as QoL and daily functioning), translation of clinical trials to the real world, clear reimbursement planning parameters, and stakeholder commitment to ensure timely access to innovative therapies.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR241
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology