Repotrectinib

• The increasing adoption of tumor-agnostic therapies has highlighted the need for universal genetic testing in oncology practices, with eight drugs now holding FDA pan-tumor approvals as of January 2025. • Healthcare providers face complex decisions regarding genetic testing methodologies, including choices between tissue and liquid biopsies, timing of collection, and interpretation of results. • Clinical implementation challenges include establishing efficient testing workflows, securing genetic counseling resources, and determining appropriate treatment sequencing in cases with limited tumor-specific data.

• The NCCN has issued significant updates across 20 different cancer types in 2024, including new tumor-agnostic approvals for repotrectinib and trastuzumab deruxtecan for solid tumors with specific genetic markers. • Multiple myeloma guidelines now recommend quadruplet regimens as standard of care for newly diagnosed patients, while CLL guidelines have shifted away from chemotherapy in favor of targeted therapies like BTK inhibitors. • Major changes in breast cancer include the addition of ribociclib for HR+/HER2- disease, while lung cancer updates feature new recommendations for osimertinib after chemoradiation in EGFR-mutated NSCLC.

• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies. • Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine. • Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes. • Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.

The five-year relative survival rate for pancreatic cancer has risen to 13%, marking the third consecutive year of improvement, yet it remains the lowest among major solid tumors.

• Memorial Sloan Kettering Cancer Center (MSK) made significant strides in cancer treatment in 2024, including novel vaccines, drugs enhancing radiation, and advanced diagnostics. • A vaccine targeting KRAS mutations in pancreatic and colorectal cancers showed promising early results in stimulating the immune system. • Imlunestrant, combined with abemaciclib, demonstrated a significant reduction in cancer progression or death in ER+, HER2- advanced breast cancer patients resistant to standard therapy. • MSK played a pivotal role in clinical trials leading to 11 FDA approvals in 2024, spanning new uses for existing drugs, effective drug combinations, and novel targeted therapies.