What treatment options are available for a patient with breast cancer who is eligible for the Patina trial?

PATINA Trial in Breast Cancer

Trial Overview and Patient Population

The PATINA trial (NCT02947685) is evaluating the combination of palbociclib, endocrine therapy (ET), and trastuzumab-pertuzumab specifically for patients with ER-positive, HER2-positive breast cancer. 1

This represents an investigational approach combining CDK4/6 inhibition with dual HER2 blockade and endocrine therapy for this unique molecular subtype.

Eligibility Criteria for PATINA-Type Patients

Based on the trial design and current treatment paradigms, patients eligible for this combination approach would have:

Disease Characteristics

• Hormone receptor-positive (ER-positive) disease - This is the defining feature that distinguishes PATINA from standard HER2-positive treatment approaches 1
• HER2-positive disease - Confirmed by FDA-approved companion diagnostic testing showing HER2 protein overexpression or HER2 gene amplification 2
• Metastatic or advanced breast cancer - The trial evaluates this combination in the metastatic setting 1

Key Molecular Features

• Dual-positive biology (ER+/HER2+) represents approximately 10-15% of breast cancers and has distinct treatment considerations 1
• These tumors may benefit from both endocrine-targeted and HER2-targeted approaches simultaneously 1

Standard Treatment Options for ER+/HER2+ Metastatic Disease

First-Line Therapy Options

For patients with ER-positive, HER2-positive metastatic breast cancer, the standard approach includes HER2-targeted therapy combined with either chemotherapy or endocrine therapy. 3

Option 1: HER2-Targeted Therapy Plus Chemotherapy

• Pertuzumab + trastuzumab + docetaxel is the standard first-line approach for HER2-positive disease, demonstrating median PFS of 18.5 months and 34% reduction in death risk 3
• This combination is appropriate regardless of hormone receptor status 3
• Continue HER2-targeted therapy until progression or unacceptable toxicity, as sequential HER2-targeted therapies remain beneficial 3

Option 2: HER2-Targeted Therapy Plus Endocrine Therapy

• Adding trastuzumab or lapatinib to an aromatase inhibitor has demonstrated progression-free survival advantage compared with AI alone in ER+/HER2+ disease 3
• This approach is particularly suitable for patients without visceral crisis or need for rapid disease control 1, 3

Monitoring Cardiac Function

• Evaluate left ventricular ejection fraction (LVEF) prior to initiation and at regular intervals during trastuzumab treatment 2
• Discontinue trastuzumab in patients receiving adjuvant therapy and withhold in patients with metastatic disease for clinically significant decrease in left ventricular function 2
• The incidence and severity of cardiomyopathy is highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens 2

CDK4/6 Inhibitor Considerations

Current Evidence in ER+/HER2- Disease

• CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) combined with endocrine therapy are standard first-line therapies for metastatic HR-positive, HER2-negative breast cancer 1
• Aromatase inhibitors in combination with CDK4/6 inhibitors have demonstrated improved progression-free survival compared to AI alone 3

PATINA Trial Context

• The PATINA trial represents an exploratory approach to determine whether CDK4/6 inhibition adds benefit to dual HER2 blockade plus endocrine therapy in the ER+/HER2+ population 1
• This combination is investigational and not yet standard of care for ER+/HER2+ disease 1

Adjuvant CDK4/6 Inhibitor Data

• The PALLAS trial showed that adding adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in early hormone receptor-positive breast cancer (iDFS at 4 years: 84.2% vs 84.5%; HR 0.96; P=.65) 4
• This negative result in the adjuvant setting highlights the importance of awaiting PATINA results before adopting this combination in ER+/HER2+ disease 4

Treatment Algorithm for ER+/HER2+ Metastatic Breast Cancer

Step 1: Confirm Molecular Status

• Biopsy metastatic lesion if easily accessible to confirm diagnosis and reassess ER and HER2 status 5
• Use FDA-approved companion diagnostic for HER2 testing 2

Step 2: Assess Disease Burden and Patient Factors

• Evaluate for visceral crisis, rapid progression, or need for rapid symptom control 1, 5
• Assess prior therapies and disease-free interval 1
• Evaluate cardiac function with LVEF assessment 2

Step 3: Select Initial Systemic Therapy

If visceral crisis or need for rapid response:

• Pertuzumab + trastuzumab + chemotherapy (typically docetaxel) 3

If no visceral crisis and slower disease progression:

• HER2-targeted therapy (trastuzumab or lapatinib) + aromatase inhibitor 3
• Consider clinical trial enrollment (such as PATINA) if available and patient meets eligibility criteria 1

Step 4: Continue HER2-Targeted Therapy Through Lines

• Continue HER2 blockade after progression on first-line trastuzumab-containing regimens 1
• Sequential HER2-targeted therapies remain beneficial 3

Critical Pitfalls to Avoid

Do Not Rely on Age Alone

• Age should not be the sole reason to withhold effective therapy in elderly patients or to overtreat in young patients 1

Do Not Omit Cardiac Monitoring

• Failure to monitor LVEF can result in serious cardiomyopathy, particularly when combining trastuzumab with anthracyclines 2
• Interrupt trastuzumab infusion for dyspnea or clinically significant hypotension 2

Do Not Discontinue HER2-Targeted Therapy Prematurely

• Continuation of HER2 blockade after progression on trastuzumab-containing regimens has shown benefit in multiple trials 1

Do Not Use CDK4/6 Inhibitors Outside Clinical Trials for ER+/HER2+ Disease

• The combination of CDK4/6 inhibitors with HER2-targeted therapy and endocrine therapy remains investigational (PATINA trial ongoing) 1
• Standard CDK4/6 inhibitor use is established only for ER+/HER2-negative disease 1, 3

Special Monitoring Requirements for Combination Therapy

For Ribociclib (if used in clinical trial setting)

• Monitor ECGs and electrolytes prior to initiation, repeat ECGs at approximately Day 14 of first cycle 6
• Monitor electrolytes at the beginning of each cycle for 6 cycles 6
• Perform liver function tests before initiating treatment, monitor every 2 weeks for first 2 cycles, then at beginning of each subsequent 4 cycles 6
• Perform complete blood count every 2 weeks for first 2 cycles, then at beginning of each subsequent 4 cycles 6

For Trastuzumab

• Monitor for infusion reactions during and within 24 hours of administration 2
• Discontinue for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome 2