Cancer healthcare system readiness: Getting EU regulation and R&D on the same path

This is a paid editorial funded by Sanofi.

Pragmatism is simple.

Pragmatism is powerful.

We are all working toward common goals in healthcare, and pragmatism can be a driver to turn ideas into a reality.

When talking about helping those living with cancer, we continuously need to evolve and find better ways of approaching clinical trials.

As the oncology treatment landscape continues to advance, the bar to making meaningful improvements versus standard of care continues to be raised. As cancer prognoses improve and we aim to catch and treat it earlier, time to achieve significant overall survival (OS)* is increasing, if ever reached. As a result, in instances where regulatory/reimbursement processes rely on OS, patient access to innovative treatments is delayed or compromised.¹

Faced with this, we need to evolve the way we choose and interpret clinical and biological endpoints to accelerate access to potential life-saving treatments and advance health through personalized medicine.

At Sanofi, we strive to modernize the treatment of cancer by working to bring new therapies for difficult-to-treat cancers and that starts with focusing our efforts to make a difference where we can. To that end, we work closely with leading cancer institutions and cooperative groups, as well as biotech companies and public-private initiatives, like the Paris-Saclay Cancer Cluster, to move the needle on oncology R&D.

We’ve centered our efforts on select hematologic malignancies and select solid tumors with critical unmet needs, including multiple myeloma (MM), acute myeloid leukemia (AML), certain types of lymphomas, as well as gastrointestinal and lung cancers.  

Not all cancers are created equal

Cancer treatment is not a one-size-fits-all approach – and neither are the endpoints that are crucial to ensure that any treatments are truly beneficial to patients. It is vital that we consider the myriad factors – such as cancer type, stage and the individual preferred outcomes for patients – when determining clinical trial endpoints.

By using certain oncology-relevant endpoints, there is an opportunity for earlier measurement of medicine efficacy. Practically speaking, this enables shorter clinical trial durations, potentially leading to quicker approval of treatments that may benefit patients.  

Minimal residual disease (MRD)** is an example of an endpoint that can provide earlier readouts.^2,3

Both Sanofi and the MM community see this as an opportunity to continue to generate data that demonstrate the correlation between certain patient-relevant endpoints, such as MRD, depth of response and longer-term clinical outcomes.^4,5,6,7

To see change, we need to be agile and pragmatic

There is a need – at a regulatory and heath technology assessment (HTA) level – to define and accelerate the qualification of patient-relevant endpoints beyond OS. This will support research into treatments that do more than prolong survival, as they may enhance quality of life and other important efficacy outcomes that really matter to patients. Access to newer, potentially more effective treatments can be accelerated if the US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) best practice is considered. The FDA ODAC recently decided there is available data to support the use of MRD as an intermediate endpoint for accelerated approval in MM clinical trials, in both newly diagnosed and relapsed/refractory disease settings.⁸

Despite the available body of evidence, the HTA agencies still consider OS the ‘gold standard’ endpoint in oncology,⁹ creating a misalignment with science and patients’ interests to get earlier access to treatments. At a national level, assessment frameworks must also evolve and place greater value on quality-of-life benefits that really matter to patients.

These are the type of patient-centered policy changes that the Europe’s Beating Cancer Plan should champion in its next phase. To stay relevant, Europe must consider pursuing the development of guidelines from regulatory, clinical and HTA perspectives to enable the use of biological and patient-centered endpoints. We must first standardize and address key uncertainties in aspects such as key methods, frequencies and sensitivity thresholds at which these new endpoints should be measured¹⁰ – and that’s not going to happen without a catalyst.

It is very clear that Europe has made huge progress and built strong foundations in its fight against cancer. Now is the time to build on it and think more broadly. Considering biological and additional patient-relevant endpoints is crucial, as we look into measuring outcomes beyond OS.

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Definitions:

* OS: Duration of patient survival from the time of treatment initiation.

** MRD: MRD refers to the small number of cancerous cells that may survive in the body after treatment. The number of surviving cells in MRD is too small for traditional tests (like biopsies or blood tests) to detect. So, a positive MRD test result indicates that cancer cells are present in the body – even at a minute level.

References:

1. European Federation of Pharmaceutical Industries and Associations, Oncology Platform. September, 2023. White Paper – Improving the understanding, acceptance and use of oncology–relevant endpoints in HTA body / payer decision-making. Accessed on 6 November, 2024: https://www.efpia.eu/media/t2nlhr0k/improving-the-understanding-acceptance-and-use-of-oncology-relevant-endpoints.pdf
2. Anderson KC, Auclair D, Kelloff GJ, et al. The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications. Clin Cancer Res. 2017;23(15):3980-3993. doi:10.1158/1078-0432.CCR-16-2895
3. Avet-Loiseau H, Ludwig H, Landgren O, et al. Minimal Residual Disease Status as a Surrogate Endpoint for Progression-free Survival in Newly Diagnosed Multiple Myeloma Studies: A Meta-analysis. Clin Lymphoma Myeloma Leuk. 2020;20(1):e30-e37. doi:10.1016/j.clml.2019.09.622
4. Perrot A, Lauwers-Cances V, Corre J, et al. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood. 2018;132(23):2456-2464. doi:10.1182/blood-2018-06-858613
5. Landgren O, Prior TJ, Masterson T, et al. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood. 2024;144(4):359-367. doi:10.1182/blood.2024024371
6. Meseha M, Hoffman J, Kazandjian D, Landgren O, Diamond B. Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions. Curr Oncol Rep. 2024;26(6):679-690. doi:10.1007/s11912-024-01537-2
7. Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4(23):5988-5999. doi:10.1182/bloodadvances.2020002827
8. FDA. April 12, 2024. Final Summary Minutes of the Oncologic Drugs Advisory Committee Meeting April 12, 2024. Accessed on 6 November, 2024: https://www.fda.gov/media/180108/download
9. Holstein SA, Suman VJ, McCarthy PL. Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials? Curr Hematol Malig Rep. 2019;14(1):31. doi:10.1007/s11899-019-0495-9
10. Myeloma Patients Europe. January, 2023. Patient and haematologist perspectives on minimal residual disease testing in myeloma. Accessed on 6 November, 2024: https://www.mpeurope.org/wp-content/uploads/2023/01/MRD-in-myeloma-Report.pdf

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