Cancer Drugs Approved With Minimal Survival Benefit: A 10-Year Evidence Review

1. Introduction

Over the past decade, a substantial proportion of cancer drugs have been approved by regulatory agencies (FDA, EMA) without robust evidence demonstrating meaningful overall survival (OS) or quality-of-life (QoL) improvement. Many approvals rely on surrogate endpoints, such as progression-free survival (PFS) or tumor response, which do not reliably predict long-term patient outcomes [1–3].

2. Drugs With Minimal or Unconfirmed OS Benefit (2015–2025)

1. Olaratumab (Lartruvo) – Advanced Soft-Tissue Sarcoma

   • Approval Basis: Accelerated approval using tumor response as a surrogate endpoint.

   • OS Evidence: Confirmatory phase III trials failed to show any OS benefit.

   • Notes: Withdrawn from clinical recommendations due to lack of demonstrated survival benefit [4].

2. Imdelltra (Amgen) – Extensive-Stage Small-Cell Lung Cancer

   • Approval Basis: Accelerated approval using surrogate outcomes.

   • OS Evidence: Later trials reported moderate OS gain (~5 months), but initial approval was not based on OS.

   • Notes: Surrogate-driven approval highlights early uncertainty regarding survival impact [5].

3. Darzalex Faspro – High-Risk Smoldering Multiple Myeloma

   • Approval Basis: Based on PFS improvements.

   • OS Evidence: No mature OS data at approval; long-term benefit remains unconfirmed [6].

4. Darzalex / Komzifti / Hyrnuo – Various Hematologic Cancers

   • Approval Basis: Mostly PFS/response endpoints.

   • OS Evidence: OS benefit unconfirmed at approval; data remains immature [6].

5. Enhertu + Perjeta (Trastuzumab Deruxtecan + Pertuzumab) – HER2+ Metastatic Breast Cancer

   • Approval Basis: Strong PFS benefits.

   • OS Evidence: OS data not mature; PFS extended from ~26.9 to 40.7 months [7].

6. Aggregate Accelerated Approvals – Multiple Indications

   • Approval Basis: Surrogate endpoints (PFS, tumor response, biomarkers).

   • OS Evidence: Fewer than 50% showed OS or QoL benefit within ~5 years; among 129 drug-indication pairs (2013–2023), only ~43% confirmed benefit in postapproval trials [1].

7. Many Cancer Drugs (US Market, 2006–2023)

• Approval Basis: Predominantly surrogate endpoints.

• OS Evidence: Less than 32% demonstrated OS improvement even post-marketing; ~78% lacked OS benefit entirely [2].

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3. Key Patterns Identified

• Surrogate Endpoints Dominate Approvals: PFS and tumor response are widely used but often fail to predict OS or QoL [1,3].

• Confirmatory Trials Lag or Fail: Many drugs remain on the market for years without demonstrating meaningful survival or QoL benefit [1,3].

• Magnitude of OS Gains is Often Small: When present, median OS improvements are ~2–3 months, sometimes statistically significant but not clinically meaningful [3].

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4. Clinical & Policy Implications

• Patient Counseling: Clinicians should communicate that drug approval does not guarantee survival benefit, and OS data may be immature.

• Policy & Reimbursement: High-cost drugs approved on surrogate endpoints raise questions about value and cost-effectiveness.

• Trial Design: Regulatory standards increasingly call for either OS or validated patient-centered endpoints at approval, or faster confirmatory trials [8].

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5. Conclusion

A large number of cancer drugs approved in the past decade demonstrate minimal or unconfirmed survival benefits, despite regulatory approvals. Many rely on surrogate endpoints and delayed confirmatory trials, emphasizing the need for rigorous evidence standards, transparent communication with patients, and critical evaluation by clinicians and policymakers.

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6. References

1. ASCO Post. Study Finds Fewer Than Half of Accelerated-Approval Drugs Show Benefit in Overall Survival or Quality-of-Life Within 5 Years. June 25, 2024. Link

2. Cancer Therapy Advisor. Most Cancer Drugs Don’t Improve Survival, Study Finds. Link

3. Gyawali B, et al. Survival Benefits of Cancer Drugs Approved by the European Medicines Agency Between 2009 and 2013. Ann Oncol. 2018;29(7):1443–1450. PubMed

4. OncLive. EMA Recommends Against Starting Olaratumab for Soft-Tissue Sarcoma. Link

5. Reuters. Amgen Drug Cuts Small-Cell Lung Cancer Death Risk by 40%. June 2025. Link

6. CureToday. Every FDA Oncology Approval From November 2025. Link

7. Reuters. FDA Approves Daiichi Sankyo’s Therapy to Treat Breast Cancer. Dec 15, 2025. Link

8. Pharmacy Times. Accelerated Approval of Cancer Drugs: Benefit or Burden? Link

9. Cancer Drugs Reimbursed with Limited Evidence on Overall Survival and Quality of Life: Swedish Medical Report