Precision, Progress, and Paradigm Shifts: The Top Oncology Approvals of 2025 (So Far)
From the first FDA-approved treatment for low-grade serous ovarian cancer to the emergence of perioperative immunotherapy in bladder and head and neck cancers, the first half of 2025 has marked a transformative period in oncology drug development.
Across tumor types, this year’s wave of approvals reflects a dual emphasis on refining targeted strategies for rare molecular subtypes and shifting curative-intent regimens toward earlier intervention. The regulatory agency’s decisions spotlight a growing clinical appetite for antibody-drug conjugates (ADCs), MEK inhibitors, and novel immunotherapy combinations—approaches that aim not only to extend survival but also to improve quality of life (QOL) and reduce treatment burdens.
In this article, I highlight the 10 most significant approvals from the first half of the year and what they mean for the future of cancer care.
Datopotamab Deruxtecan in HR+/HER2– Metastatic Breast Cancer
Approval Date: January 17, 2025
Datopotamab deruxtecan-dlnk (Datroway; Dato-DXd; Daiichi Sankyo ) became the first TROP2-directed ADC approved for patients with hormone receptor–positive/HER2-negative metastatic breast cancer following endocrine and chemotherapy failure. Backed by the phase 3 TROPION-Breast01 trial (NCT05104866), the drug (n = 365) significantly extended progression-free survival (PFS) vs chemotherapy (n = 367; HR, 0.63) and demonstrated a manageable safety profile.
“This novel ADC provides patients with metastatic breast cancer a new treatment alternative to standard chemotherapy,” said Aditya Bardia, MD, MPH, FASCO, professor in the Department of Medicine in the Division of Hematology/Oncology and director of Translational Research Integration at UCLA Health. Listen to the full OncLive® exclusive interview.
Honorable mention: Last month, Dato-DXd also won accelerated approval for use in adults with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who have previously received EGFR-directed therapy and platinum-based chemotherapy based on data from the phase 2 TROPION-Lung05 (NCT04484142) and phase 3 TROPION-Lung01 (NCT04656652) trials. With this decision, it became the first and only TROP2-directed therapy approved in the US for the treatment of lung cancer.
Mirdametinib in NF1-Associated Plexiform Neurofibromas
Approval Date: February 11, 2025
Mirdametinib (Gomekli; SpringWorks Therapeutics ) became the first and only FDA-approved treatment for adults and children aged 2 years or older with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). The ReNeu trial (NCT03962543) showed durable responses and improvements in pain and QOL.
“For this population, this is a big win,” said Christopher Moertel, MD, a pediatric neuro-oncologist; professor; director of the Pediatric Neuro-Oncology Fellowship Program in the Division of Pediatric Hematology/Oncology; medical director of Pediatric Neuro-Oncology and Neurofibromatosis Programs; co-medical director of the Katie Hageboeck Children's Cancer Research Fund Clinic; and The Kenneth and Betty Jayne Dahlberg Professor at the University of Minnesota School of Medicine. “Adult patients with NF1 have been without an FDA-approved drug for quite some time.” Listen to or read the full interview.
In another interview, our editors spoke with Rene Y. McNall-Knapp, MD, a pediatric hematologist-oncologist at the Jimmy Everest Center at Oklahoma Children’s Hospital Oklahoma University Health, who shed light on the symptom management benefits and cosmetic drawbacks often associated with NF1-associated PN therapies, as well as toxicity monitoring and management strategies.
Vimseltinib in Tenosynovial Giant Cell Tumor
Approval Date: February 14, 2025
Vimseltinib (Romvimza; Deciphera Pharmaceuticals ) is now the first systemic therapy for tenosynovial giant cell tumor (TGCT) with proven benefit in tumor reduction, function, and pain without liver toxicity—offering a non-surgical path for patients where surgery risks major disability.
"TGCT, especially the diffuse type, can be a very devastating disease for people. It's not something that generally threatens their life, but it can really alter the trajectory of their life," William Tap, MD, of Memorial Sloan Kettering Cancer Center, told OncLive. "People live with the disease for long periods of time and can have tremendous symptoms and a lot of disability from it, so to have medical options for TGCT is critical for us." Listen to the full interview in this episode of OncLive On Air.
OncLive also spoke with R. Lor Randall, MD, FACS, the David Linn Endowed Chair for Orthopaedic Surgery, as well as the chair of and a professor in the Department of Orthopaedic Surgery at the University of California Davis Comprehensive Cancer Center, who further explained how the agent stands out as an alternative to surgery for select patients with diffuse TGCT.
Cabozantinib in Advanced Pancreatic and Extrapancreatic NETs
Approval Date: March 26, 2025
With its approval in pancreatic and extrapancreatic neuroendocrine tumors (NETs), cabozantinib (Cabometyx; Exelixis ) adds a targeted therapy option for patients with progressive, well-differentiated NETs regardless of biomarker status, based on strong PFS gains reported in the phase 3 CABINET trial (NCT03375320). The HRs for PFS in the pNET and epNET cohorts were 0.22 and 0.40, respectively.
“To have an [FDA approval cover a] broad range of primary tumor sites is wonderful to see, as it also covers patients who have functional tumors or nonfunctional tumors, and those who may have somatostatin receptor–positive or –negative disease,” Jennifer Chan, MD, MPH, of Dana-Farber Cancer Institute, said in an interview with OncLive. “There weren’t many restrictions in the approval, which means that it’s [now] a standard option for a large number of patients.”
In a recent OncLive Insights series, Namrata (Neena) Vijayvergia, MD, and Thor R. Halfdanarson, MD, further discussed efficacy and safety data from the CABINET trial, how to integrate cabozantinib into the NETs treatment landscape, and provided practical insights on how to manage patients on the drug.
Perioperative Durvalumab in Muscle-Invasive Bladder Cancer
Approval Date: March 28, 2025
Findings from the phase 3 NIAGARA trial (NCT03732677) supported durvalumab (Imfinzi; AstraZeneca )’s approval as the first FDA-cleared perioperative immunotherapy in muscle-invasive bladder cancer, significantly improving survival outcomes when added to neoadjuvant chemotherapy.
"The significance of the approval of perioperative durvalumab for the treatment of patients with MIBC is that it really represents the first time that a treatment has been added to standard cisplatin-based chemotherapy in the neoadjuvant setting, which has improved outcomes," Matthew Galsky, MD, of Mount Sinai and The Tisch Cancer Institute, told OncLive. Listen to or read the full interview.
In May 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended the approval of perioperiative durvalumab in this population based on NIAGARA data.
Avutometinib Plus Defactinib in KRAS-Mutated Low-Grade Serous Ovarian Cancer
Approval Date: May 8, 2025
The co-packaged targeted therapy, avutometinib plus defactinib (Avmapki Fakzynja Co-pack), became the first-ever FDA-approved treatment for low-grade serous ovarian cancer (LGSOC)—a rare and treatment-resistant subtype—marking a major breakthrough for KRAS-mutated cases. RAMP-201 (NCT04625270) data showed that the treatment elicited an overall response rate (ORR) of 44%, which comprised a complete response (CR) rate of 3.5% and a partial response rate of 40%.
"This is the first time we have ever had an FDA approval for LGSOC, a rare variant of ovarian cancer," Bradley Monk, MD, FACOG, FACS, of Florida Cancer Specialists & Research Institute, told OncLive. "...My advice to practitioners would be [that we have to] educate each other and educate our patients about this new opportunity. In addition to my enthusiasm about the activity [of the combination] I think we have to be familiar with the most common adverse [effects]." Read the full interview.
“To have a treatment that was developed specifically for patients with LGOC targeting that MAPK pathway, [which] drives this disease for so many of our patients, it really is a game changer and something that was designed specifically for these patients," Rachel Grisham, MD, of Memorial Sloan Kettering Cancer Center, added in another interview.
Telisotuzumab Vedotin in Advanced NSCLC Eith High c-MET Overexpression
Approval Date: May 14, 2025
Telisotuzumab vedotin-tllv (Emrelis; AbbVie ) earned accelerated approval as the first treatment targeting c-MET overexpression in NSCLC, based on an ORR of 35% and a median duration of response of 7.2 months in the phase 2 LUMINOSITY trial (NCT03539536).
"People with c-MET overexpressing NSCLC have poor prognosis and limited treatment options, and [telisotuzumab vedotin] is a first-in-class ADC that can address a critical unmet need for this patient population," Jonathan Goldman, MD, of UCLA, said in a news release. In an interview with OncLive, he added "The primary end point of LUMINOSITY was the objective response rate in the c-MET–high group. It was 35%, so it was meaningfully superior to 2 other FDA-approved agents in the second-line setting." Listen to or read the full interview.
In another exclusive interview, Joshua K. Sabari, MD, of Perlmutter Cancer Center and NYU Grossman School of Medicine, underscored the following about the decision: "This is a game changer for patients. We are seeing durable responses more so than we’re seeing with docetaxel and ramucirumab."
Retifanlimab in Locally Recurrent or Metastatic Anal Cancer
Approval Date: May 15, 2025
Retifanlimab-dlwr (Zynyz; Incyte ) became the first PD-1 inhibitor approved for squamous cell carcinoma of the anal canal (SCAC) in both first-line and post-platinum settings. The POD1UM-303 trial (NCT04472429) showed improved PFS, overall survival, and ORR when added to chemotherapy.
"This FDA approval [indicates] an immunotherapy drug for the first time, and [this is] an area where there is a significant unmet need," Marwan Fakih, MD, of City of Hope, said in an exclusive interview. He noted that this represents the first phase 3 evidence supporting an immunotherapy-based regimen in SCAC, replacing the historical reliance on chemotherapy alone—typically carboplatin and paclitaxel, which had been adopted from phase 2 data rather than from randomized, controlled trials.
In another interview, Cathy Eng, MD, FACP, FASCO, of Vanderbilt-Ingram Cancer Center, added: [POD1UM-303] was the first trial to be presented to demonstrate a PFS benefit of a little over 2 months for [patients with] newly diagnosed metastatic SCAC. [Retifanlimab] is a new option [that allows us] to move IO therapy to the frontline setting."
Mitomycin Intravesical in Low-Grade NMIBC
Approval Date: June 12, 2025
Mitomycin intravesical solution (Zusduri; UGN-102; UroGen Pharma ) provides a novel chemoablative approach for low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), reducing reliance on repeated surgery. Approval followed strong CR rates and durable responses in the ENVISION trial (NCT05243550).
“The greatest implication of [this approval] is that, for the first time, we're going to have a completely novel way of treating patients with low-grade, intermediate-risk bladder cancer," William C. Huang, MD, of Tisch Hospital and NYU Langone Health, told OncLive. "It's going to be a paradigm shift for many patients from something that's primarily been surgical to something that is non-surgical and chemoablative.”
Ahead of the approval, in May 2025, the regulatory agency's Oncologic Drugs Advisory Committee had voted 5 to 4 against the risk/benefit profile of the agent in this population. Those voting against the profile noted that without a full randomized trial, it is difficult to determine the true benefit of the approach. Those who voted yes noted it was an important option for select patients with significant comorbidity and who are not ideal surgical candidates.
Perioperative Pembrolizumab Regimen in Locally Advanced HNSCC
Approval Date: June 12, 2025
Perioperative pembrolizumab (Keytruda; Merck ) became the first immunotherapy-based regimen approved for resectable head and neck squamous cell carcinoma (HNSCC) with a PD-L1 combined positive score (CPS) of 1 or higher. KEYNOTE-689 (NCT03765918) data showed that in this population, the median EFS was 59.7 months in the pembrolizumab arm vs 29.6 months in the control arm (HR, 0.70).
“These results establish that…there’s a new standard of care for patients with locally advanced, resectable head and neck cancer [and] that is neoadjuvant pembrolizumab, followed by surgery and adjuvant pembrolizumab, given concurrently [with] and after radiotherapy or chemoradiotherapy," Douglas R. Adkins, MD, of Washington University School of Medicine, Siteman Cancer Center, told OncLive. "This is the first advancement…in treatment outcomes of patients with locally advanced head neck cancer that is resectable in over 20 years.”
In another exclusive interview, Ravindra Uppaluri, MD, of Dana-Farber Cancer Institute and Brigham and Women's Hospital, added: “The significance of this [approval] is huge for patients in the field because the first time in over 20 years, there's been a change in the current paradigm for these patients [with resectable, locally advanced HNSCC."
Looking Ahead to Q3
The third quarter of 2025 is poised to bring a wave of pivotal FDA decisions that could redefine standards of care across a wide range of oncology indications—from common solid tumors to rare hematologic and pediatric malignancies.
Notable regulatory actions include several potential first-in-class therapies, such as sunvozertinib (Zegfrovy; Dizal Pharmaceutical ) for EGFR exon 20–mutant NSCLC (just approved today!) and dordaviprone for H3K27M-mutant diffuse glioma, as well as high-impact biologics like linvoseltamab-gcpt (Lynozyfic; Regeneron Pharmaceuticals, Inc. ; also approved today!) and odronextamab for relapsed/refractory hematologic cancers. Decisions are also anticipated on treatment-expanding combinations, such as belantamab mafodotin with bortezomib- or pomalidomide-based backbones in multiple myeloma and glofitamab plus GemOx in diffuse large B-cell lymphoma.
Additionally, Q3 may bring important formulation and delivery innovations—including a potential first approval for subcutaneous pembrolizumab across solid tumor indications, which could meaningfully reduce infusion burden. Other anticipated decisions, such as the approval of a shorter-acting leuprolide mesylate formulation for prostate cancer, signal continued emphasis on convenience and flexibility in cancer treatment delivery.
With all these high-stakes applications under review, the oncology pipeline shows no sign of slowing, and the outcomes of these reviews will be closely watched for their potential to address longstanding gaps in care.