INAVOLISIB TAB,ORAL

Clinical Criteria Summary

PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer
Disease detected by an FDA-approved test
Following recurrence on or after completing adjuvant endocrine therapy
Endocrine-resistant disease defined as disease progression during or within 12 months of adjuvant endocrine therapy completion
Measurable disease per RECIST v1.1 criteria
No prior therapies for advanced breast cancer (per trial inclusion)
Women with any menopausal status and men are eligible
Key exclusion: type 1 diabetes mellitus or type 2 diabetes mellitus that required ongoing treatment at the start of study treatment, metastatic breast cancer

Test fasting glucose levels (FPG or FBG) and HbA1C levels before initiating
Optimize fasting glucose prior to initiation due to potential for hyperglycemia
Verify pregnancy status in females of reproductive potential prior to initiating treatment
Mutation testing must be completed via a specific assay

9 mg orally once daily with or without food until disease progression or unacceptable toxicity
Administered in combination with palbociclib and fulvestrant
Treatment cycles are 28 days each

Monitor for hyperglycemia; initiate or optimize anti-hyperglycemic medications as clinically indicated, reserving insulin as last-line
Interrupt, reduce dose, or discontinue if severe hyperglycemia occurs
Monitor for stomatitis; consider corticosteroid-containing mouthwash; withhold, reduce dose, or permanently discontinue based on severity
Monitor for diarrhea (may be severe and result in dehydration or AKI); interrupt, reduce dose, or discontinue if severe; advise antidiarrheal treatment, increased oral fluids, and provider notification
Monitor for high-grade neutropenia due to the palbociclib component
Advise use of effective non-hormonal contraception due to embryo-fetal toxicity risk

First-line treatment for endocrine-resistant metastatic disease with PIK3CA mutations
NCCN Category 1, Preferred for HR+, HER2-, PIK3CA-mutated advanced or metastatic breast cancer
Most appropriate for patients with PIK3CA biomarkers who have not had prior exposure to CDK 4/6 inhibitors
VA Breast Cancer Clinical Pathway (VA BCCP): Has not been added to VA BCCP at this time; topic has not been reviewed; on agenda for next quarterly review

Uncontrolled hyperglycemia
Unable to evaluate and optimize fasting blood glucose
Pregnancy
Lactating
Patients with diabetes mellitus Type 1 and Type 2 requiring ongoing anti-hyperglycemic treatment were excluded from INAVO120; fasting blood glucose < 126 mg/dL and HbA1c < 6% was required prior to start

HR-positive, HER2-negative (IHC 0 or 1+ or IHC 2+/ISH-) locally advanced or metastatic breast cancer
Progressive disease on or after endocrine-based adjuvant regimen
No prior CDK4/6 inhibitor therapy (i.e. abemaciclib, ribociclib, palbociclib)
PIK3CA-mutation detected using an FDA-approved test
Inavolisib to be given in combination with palbociclib and fulvestrant

Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
Goals of care and role of Palliative Care consult have been discussed and documented

For females who can become pregnant: Pregnancy must be excluded prior to receiving inavolisib
For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for one week after stopping treatment
For females who are lactating / providing breastmilk to an infant or planning to do so: Counseling provided to avoid breastfeeding during therapy