Key FDA Oncology Approvals in 2025: Precision Therapies and New Targets

The oncology landscape in 2025 was defined by significant regulatory milestones, with the FDA approving several novel agents that reinforce the paradigm of precision medicine. This year saw the continued dominance of antibody-drug conjugates (ADCs) and the introduction of highly specific tyrosine kinase inhibitors (TKIs) that address previously difficult-to-treat mutations.

The following review highlights 4 pivotal FDA approvals from 2025 that are poised to alter clinical practice in breast cancer, non–small cell lung cancer (NSCLC), and rare tumors.

Breast Cancer: Expanding Options for HR-Positive Disease

Two major approvals in 2025 targeted hormone receptor (HR)-positive, HER2-negative breast cancer, offering new sequences for patients who have progressed on initial endocrine therapies.

Datopotamab Deruxtecan-dlnk (Datroway; Dato-DXd)

On January 17, 2025, the FDA approved Dato-DXd, a TROP2-directed ADC , for adult patients with unresectable or metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine-based therapy.¹ This approval marks the entry of TROP2-targeted ADCs into the HR-positive space.

The decision was based on results from the phase 3 TROPION-Breast01 trial (NCT05104866). The study demonstrated a statistically significant improvement in progression-free survival (PFS) for patients treated with Dato-DXd compared with investigator’s choice of chemotherapy (6.9 months vs 4.9 months; HR, 0.63; P <.0001). While overall survival data were not mature at the time of approval, the PFS benefit establishes this agent as a viable chemotherapy-sparing option in the second- or third-line setting.

Imlunestrant (Inluriyo)

Later in the year, on September 25, 2025, the FDA approved imlunestrant, a novel oral selective estrogen receptor degrader (SERD). It is indicated for the treatment of postmenopausal women and men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who have disease progression following at least one line of endocrine therapy.²

Approval was supported by the EMBER-3 trial (NCT04975308), which compared imlunestrant monotherapy against standard endocrine therapy. The trial showed that imlunestrant reduced the risk of disease progression or death by 38% in patients with ESR1 mutations Given the prevalence of ESR1 mutations as a mechanism of resistance to aromatase inhibitors, imlunestrant represents a critical oral alternative to fulvestrant injections.

Lung Cancer: Targeting HER2 Mutations

Zongertinib (Hernexeos)

On August 8, 2025, the FDA granted accelerated approval to zongertinib for adult patients with unresectable or metastatic nonsquamous NSCLC harboring HER2 (ERBB2) tyrosine kinase domain (TKD) mutations.³

Zongertinib is an oral TKI designed to selectively inhibit HER2 while sparing wild-type EGFR, potentially reducing toxicities such as rash and diarrhea commonly associated with pan-HER inhibitors. The approval was based on the Beamion LUNG-1 trial (NCT04886804). In the primary efficacy population, zongertinib elicited an objective response rate (ORR) of 75% in patients who had received prior platinum-based chemotherapy. This high response rate in a historically challenging subgroup underscores the value of genotype-directed therapy in NSCLC.

Rare Tumors: A New Standard for TGCT

Vimseltinib (Romvimza)

Addressing a rare but debilitating condition, the FDA approved vimseltinib on February 14, 2025, for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) not amenable to surgery.⁴ TGCT is a locally aggressive tumor driven by CSF1R overexpression.

The approval followed the results of the phase 3 MOTION trial (NCT05059262). Vimseltinib demonstrated a robust ORR of 40% at week 25 compared with 0% in the placebo arm (P <.0001). Furthermore, patients reported significant improvements in physical function and stiffness, validating the drug's impact on quality of life for this patient population.

REFERENCES

1. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. News release. FDA. January 17, 2025. Accessed December 16, 2025. https://tinyurl.com/2nf2nnyk

2. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly and Company. September 25, 2025. Accessed December 16, 2025. https://tinyurl.com/39fjy4n3

3. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. US FDA. August 8, 2025. Accessed December 16, 2025. https://tinyurl.com/fbakh64s

4. FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. News release. US FDA. February 14, 2025. Accessed December 16, 2025. https://tinyurl.com/49abk2wy