The U.S. Food and Drug Administration (FDA) has granted full approval to selpercatinib, marketed as Retevmo, for the treatment of patients aged 2 years and older with advanced solid tumors harboring a RET gene fusion.
The approval, granted on July 14, represents another important step toward treating cancer according to the molecular alteration driving tumor growth rather than the organ in which the disease originated.
Selpercatinib can now be used across a broad range of RET fusion–positive malignancies, including lung, thyroid, pancreatic, ovarian, and rare pediatric cancers.
A Tumor-Agnostic Milestone in Precision Oncology
Selpercatinib is a selective targeted therapy designed to inhibit abnormal RET signaling. Its full approval confirms its role as a tumor-agnostic treatment—one that may be prescribed based on a shared genomic feature across different cancer types.
Alexander Drilon, MD, Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, described the decision as a pivotal moment in precision oncology.
The approval not only validates selpercatinib as an effective targeted therapy but also expands treatment opportunities for patients with diverse tumor types driven by RET gene fusions, including those with rare cancers for which few established options may be available.
Dr. Drilon led one of the two clinical trials that supported the FDA’s decision.
From Accelerated Approval to Full Regulatory Confirmation
The FDA first granted accelerated approval to selpercatinib in 2020 for patients with advanced RET fusion–positive lung and thyroid cancers. That initial decision was based on clinical research led by Dr. Drilon and Eric Sherman, MD, a head and neck medical oncologist at MSK.
Full approval was subsequently granted for these tumor-specific indications.
The accelerated approval was later expanded to include metastatic solid tumors with RET gene fusions, regardless of their site of origin, as well as patients as young as 2 years old.
The latest regulatory action converts that tumor-agnostic indication from accelerated to full approval, confirming the clinical benefit and safety of selpercatinib for broader use.
Durable Responses Across More Than a Dozen Cancers
Clinical trial findings demonstrated meaningful and sustained activity across a wide range of advanced malignancies.
Nearly half of the patients included in the studies experienced a substantial reduction in tumor size. The objective response rate reached 47% across more than a dozen cancer types.
Responses lasted for more than two years on average, an important finding among patients with advanced disease who had already exhausted other available treatment options.
These results demonstrate that identifying the molecular driver of a tumor can uncover an effective therapeutic strategy even when the cancer originates in an uncommon site.
Understanding RET Gene Fusions
Gene fusions occur when part of one gene breaks away from its normal location on a chromosome and attaches to another gene. The resulting fusion can create a permanently activated signal that continuously instructs cells to grow and divide.
In RET fusion–positive cancers, the rearranged RET gene functions as an oncogenic driver.
Selpercatinib blocks this abnormal signal, effectively switching off the pathway that supports cancer cell growth.
Although RET gene fusions are uncommon, their identification can have major therapeutic implications. They are present in approximately 1% to 2% of lung cancers and are even less frequent in most other solid tumors.
They are considerably more common in papillary thyroid cancer, where they are found in approximately 10% to 20% of cases.
Basket Trials Open the Door Beyond Tumor Location
The full approval also highlights the growing importance of basket trials in oncology.
Unlike traditional clinical trials that enroll patients according to the organ in which the cancer developed, basket trials evaluate a treatment across multiple tumor types that share the same molecular alteration.
This approach allowed investigators to study selpercatinib in patients with different cancers linked by a common RET fusion.
According to Dr. Drilon, the approval reaffirms the value of conducting clinical trials based on tumor genetics rather than tumor location. It also demonstrates how research conducted at specialized early drug development centers can influence care for patients far beyond the institutions leading the trials.
Potential Beyond Advanced Disease
Research into selpercatinib is also moving into earlier stages of cancer.
Dr. Drilon recently published findings showing that selpercatinib substantially reduced the risk of recurrence in patients with early-stage RET fusion–positive lung cancer.
The results suggest that targeted RET inhibition may eventually play a role not only in controlling advanced disease but also in increasing the likelihood of cure for selected patients with early-stage cancer.
A Stronger Case for Comprehensive Molecular Testing
The full approval of selpercatinib reinforces the importance of comprehensive genomic testing in patients with advanced solid tumors.
Because RET fusions are rare and can occur across multiple cancer types, they may be missed unless tumors are tested using methods capable of detecting gene rearrangements.
Identifying a RET fusion can provide patients with access to a targeted treatment capable of producing durable responses, even after standard therapies have been exhausted.
The approval marks another advance in the shift toward molecularly guided cancer care, where the biology of the tumor increasingly determines the treatment strategy.
Written by Nare Hovhannisyan, MD
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