Capivasertib

Roche's PI3K inhibitor Itovebi approved by FDA for use in triple therapy for locally advanced or metastatic HR-positive, HER2-negative breast cancer with PIK3CA mutation. Phase 3 INAVO120 study showed progression-free survival more than doubled to 15 months with Itovebi compared to 7.3 months for control group. Roche predicts Itovebi sales could reach CHF 2 billion annually.

The TROPION-Breast01 phase III trial of datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in the final overall survival (OS) analysis for patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer. Despite this, the trial previously met the progression-free survival (PFS) endpoint, showing a significant improvement in PFS and patient-reported outcomes. The safety profile remained consistent with no new safety concerns. The treatment landscape's advancement with multiple antibody drug conjugates (ADCs) approved during the trial may have influenced the OS results.

TROPION-Breast01 Phase III trial of datopotamab deruxtecan did not achieve statistical significance in overall survival (OS) analysis for inoperable or metastatic HR-positive, HER2-low or negative breast cancer patients, despite meeting progression-free survival (PFS) primary endpoint. Safety profile consistent with previous analysis, with no new safety concerns. Multiple ADCs approved during trial likely affected survival results. AstraZeneca and Daiichi Sankyo continue discussions with regulatory authorities and clinical development for datopotamab deruxtecan.

Final overall survival results from TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in HR-positive, HER2-low or negative breast cancer patients, despite positive progression-free survival results. Safety profile remained consistent with no new concerns. Subsequent treatment options likely affected survival results.

Warren Kotler, a 61-year-old man with Stage 4 metastatic breast cancer, has outlived his prognosis by receiving various treatments. His oncologist suggested a new drug, capivasertib (Truqap), which could delay cancer progression but is currently approved only for women in Canada due to insufficient male participation in clinical trials. Kotler's medical team seeks compassionate use of the drug, but AstraZeneca denies coverage, citing Health Canada's approval restrictions. Despite the drug's potential benefits and similar disease biology in men and women, regulatory bodies face challenges due to the rarity of male breast cancer cases.

AstraZeneca Korea launched Truqap, the first AKT inhibitor for HR+/HER2- breast cancer, targeting PIK3CA, AKT1, or PTEN mutations. Truqap, approved in April, offers new hope for patients progressing after endocrine therapy. The CAPItello-291 study showed Truqap plus fulvestrant doubled median progression-free survival to 7.3 months. Despite financial concerns over NGS costs, global guidelines recommend mutation testing for effective treatment.

Post-hoc analysis in DESTINY-Breast12 showed CNS ORR of 82.6% in patients without prior CNS therapy and 50.0% in those with prior therapy. Safety profiles of Enhertu were consistent with previous trials, with no new concerns. ILD/pneumonitis rates were 12.9% and 16.0% in patients without and with brain metastases, respectively, with most events being low grade.

Relay Therapeutics' experimental breast cancer drug, RLY-2608, delayed tumor growth by 9 months in a trial, shrinking tumors in 75% of participants. The drug, targeting PI3Ka mutations, showed potential to replace existing treatments with less toxicity, prompting Relay to plan a pivotal trial for 2024. The study enrolled 118 patients with PI3Ka-mutated, HR-positive, HER2-negative breast cancer.