How RTOR accelerated cancer treatment development

The Real-Time Oncology Review (RTOR) pilot launched by the U.S. Food and Drug Administration (FDA) in February 2018, has had a profound impact on how — and how quickly — treatments for cancer are approved. Originally launched to review supplemental indications for existing cancer treatments, the pilot was later expanded to include new treatments known as new molecular entities (NMEs).

Under RTOR, manufacturers can get approval for a treatment within two to 24 weeks, compared to six to 10 months under any other kind of priority review. This is done through early review of key data — done in near real-time — and through simpler study design and end-point determination.¹ Using this approach, the program has vastly accelerated the approval of oncology treatments, potentially enabling these therapies to reach patients faster. But it may also increase cost. Payors need to ensure appropriate utilization to effectively manage spend on these high-cost treatments.

How RTOR Works, Its Impact

RTOR allows the FDA to access and review key data prior to official New Drug Application/Biologics License Application (NDA/BLA) submission.² The first drug to be approved through this process was Kisqali, which was approved in three weeks, and is indicated for the treatment of HR-positive, HER2-negative breast cancer in post-menopausal women whose cancer is advanced or metastatic.³

Under the same program, the agency also approved a supplemental indication for Adcetris, to be used in combination with chemotherapy for adult patients with certain types of peripheral T-cell lymphoma. It was approved in just two weeks from the date of the application.⁴

As of April 2020, the agency had approved 20 applications — including 18 supplemental indications and two NMEs — through RTOR.⁵

Supplemental indication approvals help expand the population for therapies already on the market, often quite significantly. And with the expedited review offered by RTOR, new treatments for many cancers — including those affecting large populations such as lung, hematological and breast cancer, and multiple myeloma — have been coming to market at a rapid pace. At the same time, more treatments are being developed for “niche” populations — cancers with a small number of patients. Often, companies use the program to gain a “first-to-market” advantage for their treatments, including new therapies or additional supplemental indications.

Evolving Approach to Cancer Treatment Development

Another interesting evolution in the development of cancer therapies has been the move toward tumor-agnostic treatments. Cancer works by turning off the body’s immune response, allowing it to spread unchecked. Historically, cancer treatments worked by targeting the cancerous tumors. Newer treatments are more targeted to the specific mutations that cause cancer, and work by helping the immune system identify the cancer and attack it. Such treatments are therefore not aimed at specific types of tumors but rather the mutations — and the cell pathways — that cause the tumors.

This means that unlike treatments that target a specific type of tumor, the new treatments can potentially treat a range of cancers based on specific gene mutations. This also means treatments can be tested in different patient populations with disparate cancers but with similar “expression(s)".

Selecting the right treatment for the right type of cancer often means looking for biomarkers that identify the type of mutation.

Gene-Sequencing to Ensure Appropriate Treatment, Lower Costs

Given the evolution of treatment — and the speed at which these treatments are coming to market — it is important to ensure the right patient is receiving the most appropriate treatment for their specific cancer. This is not only important to improve quality of life and outcomes but can also help reduce costs because patients do not go through ineffective treatments before being prescribed the most appropriate therapy.

Gene sequencing combined with the patient’s clinical picture can help match patients to the most appropriate clinical trials.

Broad-panel gene sequencing to map the genomic landscape of an individual’s specific type of cancer can play a critical role in this. Identifying the broader genomic landscape of a patient’s tumor earlier gives oncology providers detailed information to make timely, precise treatment decisions that are ultimately more cost-effective and deliver better quality of care.

Gene sequencing, combined with the patient’s full clinical profile, can also help match patients to the most appropriate clinical trials. RTOR has made it possible for better targeted clinical trials that are smaller in scale so that treatments can come to market faster. If a patient has obtained broad panel sequencing, it helps connect them to trials that give them access to as-yet unapproved therapies.

Value-Based Contracting

Another important consideration for payors is the “durability” of the new treatments. The simpler study design enabled by RTOR has led to much shorter research and development times and a faster path to market for many drugs. Given that many of these medications are extremely costly, it raises a question: If the treatment doesn’t work as promised, should payors be responsible for the full cost? Value-based contracts, including outcomes-based pricing agreements, can play an important role in helping ensure that patients have access to these important treatments with some value guarantee, especially in cases when they do not work as intended.

Our Transform Oncology Care program is designed to use technology and the latest genomic science to solve some of the biggest challenges in oncology management today. It uses the results of broad-panel gene sequencing tests and the latest National Comprehensive Cancer Network treatment and supportive care guidelines to help providers select the most precise, appropriate treatment regimen based on the patient’s clinical and genetic profile.

Data source, unless noted otherwise, CVS Health Enterprise Analytics, 2021.

This document contains references to brand-name prescription drugs that are trademarks or registered trademarks of pharmaceutical manufacturers not affiliated with CVS Health.

Image source: Licensed from Getty Images, 2021.