CurrentmhnPolicy CP.PHAR.430

Clinical Policy: Alpelisib (Piqray, Vijoice)

Defines medical necessity criteria, prior authorization requirements, dosing limits, and continued therapy rules for alpelisib (Piqray and Vijoice) for commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyAlpelisib (Piqray, Vijoice) coverage policy

Policy CodePolicy CP.PHAR.430

Change TypeNo material change

Effective DateJul 9, 2019

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, imaging) showing the member meets all approval criteria and dosing limits for the requested indication.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

300 mg/daymax Piqray dose

250 mg/dayadult Vijoice max

≥18min age Piqray

≥2min age Vijoice

12 monthscommercial approval dur.

Coverage and Medical Necessity Criteria

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Initial Therapy — Breast Cancer

Covered when ALL of the following are met for breast cancer (Piqray):

Breast Cancer Initial Approval: 1. Request is for Piqray; 2. Diagnosis of breast cancer; 3. Prescribed by or in consultation with an oncologist; 4. Age >= 18 years; 5. Disease has all of the following characteristics: (a) HR-positive (ER/PR-positive); (b) HER2-negative; (c) advanced (recurrent) or metastatic; (d) positive for PIK3CA mutation; 6. Piqray is prescribed in combination with fulvestrant; 7. Disease has progressed on or after an endocrine-based therapy regimen; 8. If member is premenopausal, member treated with ovarian ablation/suppression; 9. Member must use alpelisib product if available unless contraindicated or clinically significant adverse effects; 10. Request meets one of: (a) dose does not exceed 300 mg/day; or (b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit evidence).dose <= 300 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — PROS

Covered when ALL of the following are met for PROS (Vijoice):

PROS Initial Approval: 1. Request is for Vijoice; 2. Diagnosis of PIK3CA-related overgrowth spectrum (PROS); 3. Age >= 2 years; 4. Member meets one of: (a) documented PIK3CA gene mutation; OR (b) if biopsy not possible, all of: (i) congenital or early childhood onset (birth to age 8); (ii) overgrowth that is sporadic/mosaic; (iii) either any two Category A features or any one Category B feature (see Appendix E); 5. Condition is severe or life-threatening requiring systemic therapy as determined by treating physician; 6. For non-cutaneous lesions, at least one target lesion identified on imaging within the last 6 months; 7. Dose does not exceed age-specific limits: (a) age 2-5 years: 50 mg/day; (b) age 6-17 years: 125 mg/day; (c) age >=18 years: 250 mg/day.age-specific dose limits

Oral granules may be used to administer 50 mg daily only; do not combine granules and tablets to achieve other doses.

Continuation Therapy

Continued therapy criteria:

Breast Cancer Continued Therapy: 1. Currently receiving Piqray via Centene benefit, or documentation supports member has received Piqray for at least 30 days; 2. Request is for Piqray; 3. Member is responding positively to therapy; 4. If request is for a dose increase, new dose does not exceed 300 mg/day or is supported by practice guidelines or peer-reviewed literature (prescriber must submit evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN.

PROS Continued Therapy: 1. Member currently receiving Vijoice via Centene benefit or previously met initial approval or has continuity of care per state rules; 2. Request is for Vijoice; 3. Member is responding positively as evidenced by improvement on imaging, improvement in signs/symptoms/complications, or improved functional status; 4. If request is for a dose increase, new dose does not exceed age-specific maxima (age 2-5:50 mg/day; age 6-17:125 mg/day; age >=18:250 mg/day).

Imaging when required must be within the last 6 months.

Initial and continuation coverage criteria

Covered when dosing and indication match labeled and policy-described uses

Breast cancer (Piqray): Member prescribed Piqray 300 mg PO daily with food in combination with fulvestrant for indicated breast cancer; maximum dose 300 mg/day.dose limits apply

Policy language revised to include all adults regardless of gender and pre/postmenopausal status (see history).

PROS (Vijoice) initiation: Pediatric patients (2 to <18 years): start 50 mg PO daily with food; consider increase to 125 mg PO daily in patients >6 years after 24 weeks for response optimization; Adult patients: 250 mg PO daily with food. Oral granules may be used only for 50 mg daily dosing. Do not use multiple 50 mg granule packets or partial packets to achieve 125 mg or 250 mg doses; do not combine granules and tablets to achieve prescribed dose.age-based maximums: age 2-5 max 50 mg/day; age 6-17 max 125 mg/day; age >=18 max 250 mg/day

For PROS initiation, policy allows diagnosis without identified PIK3CA mutation in some situations per prior updates.

Requests for indications that are not FDA‑approved and not specifically addressed in this policy are excluded unless the provider submits sufficient documentation of efficacy and safety per the applicable off‑label use policies. See CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid) for the required off‑label evidence and documentation standards.

For Vijoice oral granules, the granule packet (single‑use 50 mg) may be used only to administer a 50 mg daily dose. Do not use multiple 50 mg oral granule packets or a partial packet of oral granules to achieve 125 mg or 250 mg doses, and do not combine oral granules and tablets to reach the prescribed dose.

Initial therapy nodes — top-level nodes

Piqray initial and PROS (Vijoice) initial - top-level grouping

Breast Cancer (Piqray) top-level: Refer to Breast Cancer Initial Approval criteria: request for Piqray, diagnosis, prescriber specialty, age >=18, disease characteristics, combination with fulvestrant, prior endocrine therapy, ovarian suppression for premenopausal women, product availability preference, dose limit 300 mg/day or guideline-supported dosing.
PROS (Vijoice) top-level: Refer to PROS Initial Approval criteria: request for Vijoice, diagnosis of PROS, age >=2, documented mutation or accepted clinical criteria when biopsy not possible, severity requiring systemic therapy, imaging requirement for non-cutaneous lesions, age-based dosing limits.

Initial therapy dosing

Piqray initial dosing: 300 mg PO daily with food in combination with fulvestrant; maximum 300 mg/day.max 300 mg/day

Piqray indication: breast cancer.

Vijoice initial dosing (pediatric): Pediatric patients (2 to <18 years): 50 mg PO daily with food; consider increase to 125 mg PO daily in patients >6 years after 24 weeks for response optimization; oral granules may be used to administer the 50 mg daily dose only.age-based limits and timing for increase

Do not use multiple 50 mg packets or partial packets to achieve 125 mg or 250 mg doses; do not combine granules and tablets.

Vijoice initial dosing (adult): Adult patients: 250 mg PO daily with food; maximum 250 mg/day.max 250 mg/day

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, imaging, or other clinical information) that demonstrates the member meets all policy approval criteria for the requested indication.

Requests for Piqray (alpelisib) or Vijoice require prior authorization with supporting clinical documentation.
Provider must include evidence supporting PIK3CA mutation status for indicated uses or the alternative diagnostic criteria for PROS when mutation testing is not available.
For breast cancer, include documentation of prior endocrine-based therapy and that Piqray will be used in combination with fulvestrant; see Appendix B for examples of prior-line endocrine therapies.

Denial Risk

Denial Risk for Missing or Non‑conforming Documentation

Failure to meet policy-specified diagnostic, prior‑therapy, or response documentation requirements may result in denial of the request.

Non‑FDA approved indications not addressed by this policy may be denied unless adequate off‑label justification and applicable off‑label policy compliance are provided.
For PROS continuation requests, lack of documentation demonstrating positive response (including improvement in PROS-related signs, symptoms, complications, or functional status) may lead to denial.
Imaging evidence for non-cutaneous PROS lesions must be within the last 6 months; absence of timely imaging may lead to denial.

Documentation Required

Required Documentation for Continuation and Prior‑Line Therapies

Provider must document continuation criteria and prior‑line therapy history when requesting ongoing treatment.

For PROS continuation: documentation should demonstrate positive clinical response such as symptom improvement, reduction in lesion burden or complications, or improved functional status.
For breast cancer: include documentation that disease progressed on or after an endocrine‑based therapy regimen (see Appendix B) and that Piqray will be given with fulvestrant as required.
The policy references prior‑line therapies in Appendix B as examples; providers should list prior endocrine and other relevant therapies used, noting that the appendix examples are not an exhaustive list.

Detailed Initial Therapy Criteria

Initial therapy nodes — 2 top-level nodes

Initial therapy grouping: Two top-level initial therapy requirement sets must be evaluated separately: (1) Breast Cancer (Piqray) initial criteria; (2) PROS (Vijoice) initial criteria. Approval requires all elements within the applicable set be met.

Operational note: Prescriber specialty, mutation documentation, age, combination therapy and dosing limits must be documented on requests per respective criteria sets.

Initial therapy dosing — labeled rules

Labeled initial dosing and formulation rules: Apply labeled dosing by indication and age: Piqray 300 mg PO daily with food (breast cancer); Vijoice pediatric start 50 mg PO daily with food (oral granules allowed only for 50 mg), consider increase to 125 mg PO daily in patients >6 years after 24 weeks; Vijoice adult 250 mg PO daily with food. Do not combine oral granules and tablets or use multiple 50 mg granule packets to achieve higher doses.follow labeled maximums

Oral granules are single-use for 50 mg dosing only.

Criteria for Continued Therapy and Reauthorization

Continuation rules — top-level nodes

Continuation top-level nodes: Organize continuation criteria into two top-level nodes: (1) Piqray continuation for breast cancer; (2) Vijoice continuation for PROS. Each node contains requirements for current therapy status, documented clinical response, and dose increase limits.

Operational continuation note: Continuation approval requires documentation of current therapy or prior approval and evidence of clinical benefit; dosing increases capped by labeled maxima unless guideline-supported evidence is provided.

Continuation therapy — documentation and expectations

Piqray continuation details: 1. Member currently receiving Piqray via Centene benefit or has documentation of >=30 days on therapy; 2. Request is for Piqray; 3. Member is responding positively to therapy; 4. Dose increase requests: new dose must not exceed 300 mg/day or be supported by practice guidelines/peer-reviewed literature (prescriber must submit evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN.

Vijoice continuation details: 1. Member currently receiving Vijoice via Centene benefit or previously met initial approval or has continuity of care; 2. Request is for Vijoice; 3. Member is responding positively as evidenced by improvement on imaging, signs/symptoms/complications, or functional status; 4. Dose increases must not exceed age-specific maxima (age 2-5:50 mg/day; age 6-17:125 mg/day; age >=18:250 mg/day).

Imaging when required must be within the last 6 months; policy history clarifies continuation expectations for PROS.

Continuation Therapy — duplicate/summary

Continued therapy criteria:

Breast Cancer Continued Therapy (summary): 1. Currently receiving Piqray via Centene benefit or documented >=30 days on therapy; 2. Request is for Piqray; 3. Positive clinical response documented; 4. Dose increase requests must adhere to 300 mg/day maximum or be guideline-supported.

PROS Continued Therapy (summary): 1. Currently receiving Vijoice via Centene benefit or previously met initial approval or under continuity of care; 2. Request is for Vijoice; 3. Positive clinical response documented (imaging, signs/symptoms, or functional improvement); 4. Dose increase requests must not exceed age-specific maxima (2-5:50 mg/day; 6-17:125 mg/day; >=18:250 mg/day).

Imaging must be within the last 6 months when required.

Sequencing and Step Therapy Requirements

Step	Requirement	Failure / Prior-line requirement	Notes
1	Piqray must be prescribed in combination with fulvestrant.	Use after progression on or after an endocrine‑based therapy regimen.	Therapeutic alternatives and recommended endocrine agents (including fulvestrant) are listed in Appendix B; prescriber must follow FDA‑approved or NCCN‑recommended regimens.

Step	Policy reference	Explicit algorithm included?	Notes
1	Policy references prior‑line therapies for breast cancer and includes examples of CDK4/6 inhibitors in Appendix B.	No — the document does not specify an exhaustive or prescriptive step‑therapy algorithm in the cited sections.	Appendix B lists therapeutic alternatives and example endocrine regimens; examples of CDK4/6 inhibitors were added to Appendix B in 3Q2023 updates.

Dosing Maximums and Quantity Limits

Piqray — maximum 300 mg (per labeled)

ProductPiqray (alpelisib)

Maximum daily dose300 mg per day (two 150 mg tablets)

Indication contextAdults with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer when used in combination with fulvestrant

Vijoice (age 2-5) — 50 mg maximum

ProductVijoice (alpelisib) — pediatric ages 2–5

Maximum daily dose50 mg per day (1 tablet or 1 oral granules packet)

Formulation noteOral granules single-use packet available as 50 mg; granules may be used only for 50 mg dosing

Vijoice (age 6-17) — 125 mg maximum

ProductVijoice (alpelisib) — pediatric ages 6–17

Maximum daily dose125 mg per day (1 tablet)

Dose escalationConsider increase to 125 mg after 24 weeks in patients >6 years for response optimization (start at 50 mg)

Vijoice (age ≥18) — 250 mg maximum

ProductVijoice (alpelisib) — adults (≥18 years)

Maximum daily dose250 mg per day (two 125 mg tablets)

AdministrationOral dosing with food

Alpelisib (Piqray, Vijoice) — per labeled maximum by age group

DrugAlpelisib (Piqray, Vijoice)

Maximum by indication/agePiqray (breast cancer, adults): 300 mg/day; Vijoice (PROS): age 2–5 = 50 mg/day; age 6–17 = 125 mg/day; age ≥18 = 250 mg/day

Formulation constraintsOral granules may be used only for 50 mg dosing; do not combine granules and tablets or use multiple 50 mg packets to reach higher doses

Key Terms and Definitions

PROS — definition of PIK3CA‑related overgrowth spectrum

TermPIK3CA‑related overgrowth spectrum (PROS)

DefinitionA group of disorders with congenital or early childhood onset mosaic overgrowth and vascular/epidermal malformations; includes syndromes such as CLOVES, CLAPO, and others

Clinical features sourceSee Appendix D and Appendix E for PROS subdivisions and NIH-recommended clinical features

PIK3CA mutation — requirement/preference for documented genetic evidence

RequirementDocumented PIK3CA gene mutation is required for Piqray breast cancer indication and is preferred evidence for Vijoice (PROS)

Alternative when biopsy not possibleFor PROS, if biopsy cannot confirm mutation, clinical criteria may be used: congenital/early childhood onset, sporadic/mosaic overgrowth, plus specified Category A/B features

Testing notePIK3CA mutation should be detected by an FDA‑approved test for the breast cancer indication

PROS short label — PIK3CA-related overgrowth spectrum description

Short labelPIK3CA-related overgrowth spectrum (PROS)

Concise descriptionDisorders caused by somatic PIK3CA mutations resulting in segmental overgrowth with vascular and soft tissue anomalies

Age range relevancePROS may present congenitally or in early childhood; Vijoice indicated for patients ≥2 years with severe manifestations requiring systemic therapy

Background and Clinical Information

Alpelisib is a PI3K alpha inhibitor marketed as Piqray and Vijoice. Piqray is FDA‑approved for adults with HR‑positive, HER2‑negative, PIK3CA‑mutated advanced or metastatic breast cancer to be used in combination with fulvestrant after progression on or after endocrine therapy; the labeled regimen for this indication is 300 mg PO once daily with food (maximum 300 mg/day). Vijoice is indicated for severe manifestations of PIK3CA‑related overgrowth spectrum (PROS) in patients aged ≥2 years, with age‑based dosing and an oral granule formulation available as a single‑use 50 mg packet in addition to tablets.

Site of Care and Administration

Note

Oral administration with food — site of care not restricted

Alpelisib (Piqray/Vijoice) is administered orally with food; the policy does not restrict site of care and oral dosing is appropriate for home administration.

Piqray: 300 mg PO daily with food (breast cancer).
Vijoice: pediatric and adult oral dosing given with food; oral granules allowed for 50 mg dosing only.

Policy Summary

Payermhn

PolicyAlpelisib (Piqray, Vijoice) coverage policy

Policy CodePolicy CP.PHAR.430

Change TypeNo material change

Effective DateJul 9, 2019

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, imaging) showing the member meets all approval criteria and dosing limits for the requested indication.

SourceLink

On This Page

PROS continuation: Continuation may require demonstration of positive response including improvement in PROS-related signs, symptoms, complications, or functional status; imaging may be required within the last 6 months.documented clinical benefit

Policy updated to specify response and imaging time window.

Do not combine granules and tablets to achieve prescribed dose.