Inavolisib

FDA approved subcutaneous nivolumab for solid tumors, supported by CheckMate-67T trial. Tislelizumab approved for gastric/GEJ cancers, based on RATIONALE-305 trial. 2024 saw breast cancer advancements, including inavolisib and ribociclib approvals. ctDNA emerged as a biomarker in HER2+ breast cancer, per DAPHNe trial findings.

In 2024, the FDA approved over 60 oncology therapies, including 11 first-in-class drugs. Highlights include Revumenib and Zolbetuximab for leukemia and gastric cancer, respectively, and new treatments targeting HER2, PD-L1, and ALK with improved efficacy and reduced toxicity. The approvals also featured novel strategies like bispecific antibodies and CAR T-cell therapies, alongside new indications for existing drugs.

Allosteric inhibitors like STX-478 and RLY-2608 show promise in targeting PIK3CA mutations in breast cancer, offering better safety and efficacy by selectively inhibiting mutant PI3Kα, reducing toxicities seen with orthosteric inhibitors.

Oral targeted therapies improve patient experience by addressing actionable mutations, influencing prognosis discussions and treatment planning. INAVO120 trial's efficacy and safety data led to approval, with inavolisib's PI3Kα specificity impacting its safety and efficacy. Precision medicine drives earlier targeted therapy combinations, as seen in ELEVATE, ELECTRA, and CAPItello-292 trials.

In 2024, significant advancements in breast oncology included FDA approvals for inavolisib, ribociclib, Tepylute, and tepylute; olaparib showing survival benefits; I-SPY 2.2 trial improving outcomes with precision medicine; TNBC vaccine research; vepdegestrant demonstrating clinical activity; neoadjuvant/adjuvant pembrolizumab improving survival in early-stage TNBC; GLP-1 agonists' potential role in breast cancer care; and T-DXd showing survival benefits in HR+/HER2-low breast cancer.

RLY-2608, an oral, mutant-selective PI3Kα allosteric inhibitor, addresses off-target toxicities of current modulators, currently in Ph. I for HR+/HER2- breast cancer treatment.

MSKCC advanced cancer treatments in 2024 include new surgical techniques, vaccines, drugs enhancing radiation, and diagnostic tools. The FDA approved 11 drugs based on MSK's pivotal clinical trials, covering new uses for existing drugs, effective drug combinations, engineered cell therapies, and novel targeted therapies. Key developments include a KRAS vaccine for pancreatic and colorectal cancer, combination drug-radiation treatment for basal cell carcinoma, noninvasive E-nose for lung cancer detection, improved transplant success with partially matched donors, exercise impact on prostate cancer biomarkers, new imaging for lung and prostate cancers, TIL therapy for non-small cell lung cancer, robotic neurosurgery for spinal tumors, avoiding surgery for HPV throat cancer with innovative radiation, imlunestrant for ER+, HER2- advanced breast cancer, mRNA vaccine for pancreatic cancer, and immunotherapy for rectal cancer. FDA approvals included tepotinib for METex14 lung cancer, CAR T treatment for mantle cell lymphoma, selpercatinib for RET-linked thyroid cancer, repotrectinib for NTRK fusion cancers, adagrasib with cetuximab for KRAS-G12C colorectal cancer, afamitresgene autoleucel for synovial sarcoma, vorasidenib for IDH glioma, inavolisib with fulvestrant and palbociclib for breast cancer, revumenib for KMT2A leukemia, zanidatamab for HER2 biliary tract cancer, and zenocutuzumab for NRG1 fusion pancreatic and lung cancers.

FDA approved inavolisib with palbociclib and fulvestrant for HR+/HER2- metastatic breast cancer with PIK3CA mutation in Oct 2024, highlighting progress in precision medicine.

At the 2024 San Antonio Breast Cancer Symposium, experts discussed FDA approvals for ribociclib and inavolisib in HR+/HER2- BC, emphasizing treatment optimization, clinical trial design, and addressing ovarian/reproductive toxicities. Ribociclib's approval was based on NATALEE trial data showing improved invasive disease-free survival (iDFS) with safety concerns. Inavolisib, targeting PIK3CA mutations, showed improved progression-free survival (PFS) with post-marketing commitments for further evaluation. The session highlighted the need for comprehensive data analysis and monitoring of fertility impacts.

Recent advancements in sequencing targeted therapies are reshaping HR-positive, HER2-negative metastatic breast cancer management, emphasizing the critical role of NGS in personalizing treatment decisions. Key factors include considering CDK 4/6 inhibitors, biomarker assessment, and sequencing new therapies like inavolisib and capivasertib. Trials such as SOLAR-1, INAVO120, and CAPItello-291 highlight improved progression-free survival and tolerable adverse effects. NGS is crucial for identifying PIK3CA/AKT mutations to determine optimal frontline and second-line treatments.