Palbociclib (Ibrance)

How Palbociclib Works

Understanding the Cell Cycle

To understand how palbociclib works, you need to know about the cell cycle - the process cells go through to divide and multiply:

1. G1 phase: Cell grows and prepares to copy its DNA
2. S phase: DNA is copied (synthesis)
3. G2 phase: Cell prepares to divide
4. M phase: Cell divides into two cells (mitosis)

The checkpoint problem: For a cell to move from G1 to S phase (the point of no return for cell division), it needs specific "green light" signals. Cancer cells have defects that allow them to bypass these checkpoints and divide uncontrollably.

CDK4/6: The Cell Cycle Accelerators

Cyclin-dependent kinases 4 and 6 (CDK4/6) are enzymes that act like accelerator pedals for the cell cycle:

• Normal cells: CDK4/6 are carefully regulated, only active when cell division is needed
• HR+ breast cancer cells: Estrogen signaling causes overactivity of CDK4/6, driving excessive cell division
• The mechanism: CDK4/6 phosphorylate (add phosphate groups to) the retinoblastoma protein (Rb)
• Result: Phosphorylated Rb releases a transcription factor (E2F) that turns on genes needed for DNA synthesis
• Outcome: Cell moves from G1 to S phase and divides

Why Palbociclib is Combined with Hormone Therapy

Palbociclib is NEVER used alone - it's always combined with endocrine (hormone) therapy like letrozole, anastrozole, or fulvestrant. Here's why:

• Synergistic effect: Hormone therapy blocks estrogen signaling from the top, palbociclib blocks CDK4/6 downstream - attacking the same pathway at two points
• Better efficacy: Studies show combination therapy is far superior to either drug alone
• Delays resistance: Using two mechanisms makes it harder for cancer to develop resistance
• HR+ dependency: Palbociclib works best in hormone receptor-positive cancers where estrogen drives CDK4/6 activity

FDA-Approved Uses

Palbociclib is FDA-approved for HR-positive, HER2-negative advanced or metastatic breast cancer in three specific settings:

1. Initial Endocrine-Based Therapy (First-Line)

• Combination: Palbociclib + aromatase inhibitor (letrozole or anastrozole)
• Indication: Postmenopausal women (or men) with newly diagnosed advanced/metastatic HR+/HER2- breast cancer
• For premenopausal women: Add ovarian suppression (goserelin or leuprolide)
• PALOMA-2 trial: Palbociclib + letrozole vs. letrozole alone
  • Median progression-free survival: 27.6 months vs. 14.5 months (13-month improvement!)
  • This made palbociclib + AI the standard first-line treatment

2. Disease Progression on Endocrine Therapy (Second-Line)

• Combination: Palbociclib + fulvestrant
• Indication: Women whose disease progressed after prior endocrine therapy
• Any menopausal status (post-, pre-, or perimenopausal with ovarian suppression)
• PALOMA-3 trial: Palbociclib + fulvestrant vs. fulvestrant alone
  • Median progression-free survival: 11.2 months vs. 4.6 months (significant improvement)
  • Also showed overall survival benefit (35 vs. 28 months)

3. Men with HR+/HER2- Breast Cancer

• Palbociclib approved for men in combination with endocrine therapy
• Male breast cancer is rare (1% of all breast cancers) but usually HR-positive
• Same dosing and effectiveness as in women

Important: What Palbociclib is NOT Approved For

• NOT for early-stage breast cancer (only advanced/metastatic)
• NOT for triple-negative breast cancer (lacks hormone receptors)
• NOT for HER2-positive breast cancer (different treatments preferred)
• NOT as monotherapy (always requires hormone therapy partner)

Dosing and Administration

Standard Dosing

• Starting dose: 125 mg once daily
• Schedule: 3 weeks on, 1 week off
  • Days 1-21: Take palbociclib 125 mg daily
  • Days 22-28: Rest week (NO palbociclib)
  • Day 29: Start next cycle
• Cycle length: 28 days
• Duration: Continue until disease progression or unacceptable toxicity (can be years)

Available Strengths

• 75 mg capsules (light orange)
• 100 mg capsules (dark orange)
• 125 mg capsules (blue)

How to Take Palbociclib

• With food: Take with a meal (breakfast or dinner, be consistent)
  • Food increases absorption and reduces nausea
  • Taking with food is REQUIRED, not optional
• Swallow whole: Do not chew, crush, or open capsules
  • If capsule is broken or cracked, do not take it
  • Wear gloves if handling broken capsules
• Same time each day: Choose morning or evening, be consistent
• Do not take with grapefruit: Grapefruit juice increases palbociclib levels significantly (see interactions)

Missed Dose

• If you vomit after taking palbociclib, do NOT take another dose that day
• If you miss a dose or forget, skip it - do NOT double up
• Take the next scheduled dose at the regular time
• The one-week break is mandatory - never skip the rest week

Dose Reductions for Neutropenia (Very Common)

Dose reductions are VERY common with palbociclib due to low white blood cell counts (neutropenia). The table below shows the dose reduction schedule:

When to Hold or Reduce Dose (Based on Blood Counts)

Dose Adjustments for Drug Interactions

• Strong CYP3A inhibitors (clarithromycin, ketoconazole, ritonavir):
  • Avoid if possible
  • If unavoidable, reduce palbociclib to 75 mg daily
• Moderate CYP3A inhibitors (erythromycin, fluconazole, diltiazem):
  • Reduce palbociclib to 75 mg daily
• Strong CYP3A inducers (rifampin, phenytoin, St. John's wort):
  • Avoid - they decrease palbociclib levels significantly

Side Effects

Very Common Side Effects (>20%)

1. Neutropenia (Low White Blood Cells) - 80-85%

The hallmark and dose-limiting toxicity of palbociclib.

• Incidence:
  • Any grade: 80-85%
  • Grade 3-4 (ANC <1000): 60-65%
• Timing: Typically lowest at day 15 of each cycle (called "nadir")
• Reversible: Counts recover during the week off (days 22-28)
• Rarely causes infections: Despite very low counts, fever and serious infections are uncommon (1-5%)
• Monitoring:
  • CBC at start of each cycle (day 1)
  • CBC on day 15 of first 2 cycles
  • Additional CBCs if neutropenia develops
• Management:
  • Dose hold if ANC <1000
  • Dose reduction if Grade 3-4 neutropenia persists
  • G-CSF (Neupogen, Neulasta) rarely needed but can be used

2. Fatigue (37-41%)

• Most common symptomatic side effect
• Usually mild to moderate (Grade 1-2)
• May worsen when counts are lowest (day 15)
• Management:
  • Prioritize activities, rest when needed
  • Light exercise if able (improves energy)
  • Check for anemia (may need treatment)
  • Rarely requires dose reduction

3. Nausea (25-35%)

• Usually mild and manageable
• Most common in first few cycles, improves over time
• Management:
  • Take with food (required anyway)
  • Anti-nausea medication as needed (ondansetron, prochlorperazine)
  • Eat small, frequent meals
  • Avoid greasy, spicy foods

4. Infections (25-31%)

• Most are minor: upper respiratory infections, urinary tract infections
• Serious infections uncommon despite low counts
• Monitor for: Fever ≥100.4°F (38°C), cough, burning with urination, unusual fatigue
• When to call: Fever, signs of infection when ANC is low

Common Side Effects (10-25%)

Anemia (Low Red Blood Cells) - 24-28%

• Grade 3-4: 5-6%
• Causes fatigue, shortness of breath
• May need transfusion or erythropoietin if severe
• Check CBC regularly

Thrombocytopenia (Low Platelets) - 16-20%

• Usually mild (Grade 1-2)
• Grade 3-4: 2-3%
• Increases bleeding/bruising risk
• Hold palbociclib if platelets <50,000

Stomatitis (Mouth Sores) - 17-28%

• Usually mild
• More common with fulvestrant combination
• Management:
  • Salt water rinses (1 tsp salt in 1 cup water, 4-6 times daily)
  • Avoid alcohol-containing mouthwashes
  • Soft, bland diet if painful
  • Magic mouthwash if severe

Diarrhea (21-24%)

• Usually mild to moderate
• Management:
  • Loperamide (Imodium) as needed
  • Stay hydrated
  • BRAT diet if severe

Vomiting (16-17%)

• Less common than nausea
• Manage with anti-emetics
• If persistent, may need dose reduction

Rash (12-17%)

• Usually mild, not severe
• May be dry skin or mild dermatitis
• Moisturize regularly, avoid harsh soaps

Alopecia (Hair Loss) - 12-18%

• Usually mild hair thinning, NOT complete hair loss
• Much less severe than chemotherapy
• Hair typically remains

Decreased Appetite (15-16%)

• Often related to nausea or fatigue
• Eat small, frequent, high-calorie meals
• Nutritional supplements if needed

Less Common But Serious Side Effects

Pulmonary Embolism (PE) - 1-5%

• Blood clot in lungs - can be life-threatening
• Higher risk than general population
• Symptoms: Sudden shortness of breath, chest pain, cough, rapid heart rate
• Action: Go to ER immediately if symptoms occur
• May need anticoagulation (blood thinners)

Hepatotoxicity (Liver Problems) - Rare

• Elevated liver enzymes in 5-10%
• Usually mild, reversible
• Monitor liver function before each cycle
• Hold or reduce dose if significant elevation

Interstitial Lung Disease (ILD) / Pneumonitis - Very Rare (<1%)

• Inflammation of lung tissue
• Symptoms: New/worsening cough, shortness of breath, difficulty breathing
• Discontinue palbociclib if diagnosed
• May require steroids

Side Effects You DON'T Get with Palbociclib

Unlike chemotherapy, palbociclib does NOT typically cause:

• Complete hair loss (alopecia)
• Severe nausea/vomiting
• Peripheral neuropathy (nerve damage)
• Hand-foot syndrome
• Kidney damage

Understanding and Managing Neutropenia

Since neutropenia is THE defining side effect of palbociclib, it deserves special attention.

What is Neutropenia?

Neutrophils are white blood cells that fight bacterial infections. Neutropenia means low neutrophil count.

• Normal ANC: 1,500-8,000 cells/mm³
• Grade 1: 1,000-1,500 (mild)
• Grade 2: 500-1,000 (moderate)
• Grade 3: 500-1,000 (severe)
• Grade 4: <500 (life-threatening risk)

Neutropenia Pattern with Palbociclib

1. Day 1 (start of cycle): Counts usually normal or near-normal
2. Day 15 (nadir): Counts at their lowest point
3. Days 22-28 (week off): Counts recover
4. Day 1 of next cycle: Counts back to starting point or close

Monitoring Schedule

• Before starting palbociclib: Baseline CBC
• Day 1 of each cycle: CBC (before taking palbociclib)
• Day 15 of cycles 1 and 2: CBC to check nadir
• As needed: Additional CBCs if neutropenia develops
• After dose holds: Weekly CBC until recovery

What to Do About Neutropenia

Prevention

• Good hand hygiene
• Avoid sick people when counts are low
• Practice food safety
• Take temperature if feeling ill

Treatment Options

• Dose reduction: Most common approach, very effective
• Dose hold: Until counts recover to ≥1000
• G-CSF (growth factor):
  • Filgrastim (Neupogen) or pegfilgrastim (Neulasta)
  • Stimulates white blood cell production
  • Used if recurrent Grade 3-4 neutropenia and doctor wants to maintain dose
  • Not routinely needed
• Antibiotics: If fever develops (febrile neutropenia)

When to Call Your Doctor

Monitoring During Treatment

Before Each Cycle (Day 1)

Day 15 of First 2 Cycles

• CBC to assess nadir (lowest point) of blood counts
• Helps predict pattern for future cycles
• May continue day 15 monitoring in later cycles if needed

Tumor Response Assessment

• CT scans: Every 2-3 months (8-12 weeks) initially
• Frequency may decrease: To every 3-4 months if stable
• Tumor markers: If elevated at baseline (CA 15-3, CA 27.29)
• Bone scans: If bone metastases present

Other Monitoring

• Symptom assessment: At each visit
• Pregnancy tests: For premenopausal women (palbociclib can harm fetus)
• EKG: Baseline and as needed (QT prolongation possible but rare)

Drug Interactions

Palbociclib is metabolized primarily by CYP3A, so drugs that affect CYP3A can significantly alter palbociclib levels.

Strong CYP3A Inhibitors - AVOID or Reduce Dose

Moderate CYP3A Inhibitors - Reduce Dose

• Reduce palbociclib to 75 mg daily if unavoidable
• Examples:
  • Erythromycin
  • Fluconazole
  • Diltiazem, verapamil
  • Dronedarone
  • Aprepitant

Grapefruit - AVOID COMPLETELY

Strong CYP3A Inducers - AVOID

Palbociclib as an Inhibitor

• Palbociclib weakly inhibits CYP3A
• May increase levels of sensitive CYP3A substrates:
  • Midazolam
  • Certain statins (simvastatin, lovastatin)
• Monitor for increased effects/toxicity of these drugs

No Significant Interactions With

• Endocrine therapies (letrozole, anastrozole, fulvestrant, exemestane, tamoxifen)
• Proton pump inhibitors (omeprazole, lansoprazole)
• Most common pain medications
• Most chemotherapy drugs (though rarely combined)

Practical Interaction Management

• Before starting palbociclib: Review ALL medications, supplements, herbals with oncologist
• Tell all doctors: You're on palbociclib before they prescribe new drugs
• Avoid OTC supplements: Especially St. John's wort
• If you need antibiotics: Azithromycin is safer than clarithromycin
• If you need antifungals: Fluconazole requires dose reduction; topical better if possible

How Well Does Palbociclib Work?

First-Line Treatment (PALOMA-2 Trial)

Second-Line Treatment (PALOMA-3 Trial)

What These Results Mean

• Major advancement: Palbociclib approximately doubles the time without disease progression
• Delays chemotherapy: Patients can stay on oral, better-tolerated therapy longer before needing chemo
• Quality of life: Better side effect profile than chemotherapy
• Now standard of care: CDK4/6 inhibitors are recommended as first-line for most patients with HR+/HER2- advanced breast cancer

Who Benefits Most?

• HR+/HER2- disease: Essential (palbociclib doesn't work in triple-negative or HER2+ cancer)
• De novo metastatic or recurrent: Both benefit
• Bone-only or visceral disease: Both benefit
• All lines of therapy: First-line shows biggest benefit, but second-line also effective
• Men: Same benefit as women (small numbers, but data suggests equivalent)

Special Populations

Premenopausal Women

• Require ovarian suppression: Goserelin (Zoladex) or leuprolide (Lupron)
• Ovarian suppression converts premenopausal women to "medically postmenopausal" state
• Then combine palbociclib with aromatase inhibitor or fulvestrant
• PALOMA-3 included premenopausal women (all received ovarian suppression)
• Same effectiveness as postmenopausal women

Pregnancy and Breastfeeding

• Pregnancy: Palbociclib can cause fetal harm
  • Effective contraception REQUIRED during treatment
  • Continue contraception for 3 weeks after last dose
  • Verify negative pregnancy test before starting
• Breastfeeding: Do not breastfeed during treatment and for 3 weeks after last dose
• Male patients: Use contraception if partner is of childbearing potential
• Fertility: May impair fertility in both men and women

Elderly Patients

• No dose adjustment needed based on age alone
• Studies included patients up to age 89
• Median age in trials: ~60 years
• Effectiveness similar across age groups
• May need closer monitoring for side effects

Hepatic Impairment (Liver Problems)

• Mild impairment (Child-Pugh A): No dose adjustment needed
• Moderate impairment (Child-Pugh B): Reduce to 75 mg daily
• Severe impairment (Child-Pugh C): Reduce to 50 mg daily (not a standard capsule strength, so challenging)
• Monitor liver function regularly

Renal Impairment (Kidney Problems)

• No dose adjustment needed for any degree of renal impairment
• Palbociclib not significantly eliminated by kidneys
• Can use in dialysis patients (limited data)

Men with Breast Cancer

• Same indications, dosing, and effectiveness as women
• Male breast cancer is 90% HR-positive
• Combine with aromatase inhibitor or fulvestrant
• May also need LHRH agonist to lower testosterone

Comparing CDK4/6 Inhibitors

Which CDK4/6 Inhibitor to Choose?

• All three are effective - no clear winner in head-to-head comparisons
• Palbociclib advantages:
  • Most clinical experience (first to market)
  • Well-established safety profile
  • Less GI toxicity than others
  • Once-daily dosing
• Consider alternatives if:
  • Abemaciclib: Brain metastases (better CNS penetration), can't tolerate neutropenia
  • Ribociclib: Strong OS data important to patient
• Choice often based on: Insurance coverage, physician experience, side effect profile preferences

Living with Palbociclib Treatment

Taking Your Medicine

• Set a daily alarm: Take at same time each day
• Use a pill organizer: Fill for the 21-day on period
• Mark your calendar: Clearly note week off (days 22-28)
• Take with food: Breakfast or dinner, be consistent
• No grapefruit: Ever, in any form
• Store properly: Room temperature, away from moisture
• Refill early: Order 1 week before running out (expensive, may take time)

Managing Fatigue

• Expect fatigue, especially around day 15 when counts are lowest
• Plan important activities for early in the cycle when energy better
• Light exercise if able (actually improves fatigue)
• Short naps okay, but maintain sleep schedule
• Ask for help with tasks when needed
• Report severe fatigue (may indicate anemia)

Preventing Infections

• Hand hygiene: Wash hands frequently, especially before eating
• Avoid sick people: Especially when counts are lowest (around day 15)
• Food safety:
  • Cook meat thoroughly
  • Wash fruits and vegetables
  • Avoid raw seafood, unpasteurized dairy
• Dental care: Soft toothbrush, gentle flossing; tell dentist before procedures
• Avoid crowds: When counts are low
• Get vaccinations: Flu shot, COVID vaccine (inactivated vaccines safe)
• Keep thermometer handy: Check temperature if feeling ill

Managing Nausea

• Take with food (required anyway)
• Eat smaller, more frequent meals
• Avoid greasy, spicy, or strong-smelling foods
• Ginger tea or ginger candies may help
• Stay hydrated
• Take anti-nausea medication as prescribed
• Usually improves after first few cycles

Mouth Care

• Rinse mouth with salt water 4-6 times daily (especially after meals)
• Use soft toothbrush
• Avoid alcohol-containing mouthwashes
• Keep mouth moist (water, ice chips, sugar-free gum)
• Avoid spicy, acidic, or rough foods if mouth sores develop

When to Call Your Doctor

Call During Office Hours for:

• Moderate fatigue interfering with daily activities
• Persistent nausea
• Mouth sores preventing eating
• Rash or skin changes
• Any new or worsening symptoms
• Questions about medications or side effects

Cost and Financial Assistance

Medication Cost

• Average wholesale price: $13,000-14,000 per month (per cycle)
• Annual cost: $156,000-168,000 if taken continuously
• No generic available: Palbociclib is still under patent protection
• All strengths same price: 75 mg, 100 mg, and 125 mg capsules cost the same per capsule

Insurance Coverage

• Generally covered: Most insurance covers for FDA-approved indications
• Prior authorization required: Oncologist must document HR+/HER2- status and indication
• Medicare Part D: Covered, though out-of-pocket can be substantial
• Specialty pharmacy: Usually requires specialty pharmacy (not retail pharmacy)

Financial Assistance Programs

Pfizer Oncology Together Co-Pay Savings Program

• For commercially insured patients (NOT Medicare/Medicaid)
• Can reduce out-of-pocket to as low as $0 per month
• Phone: 1-877-744-5675
• Website: IBRANCEhcp.com/cost-support

Pfizer Patient Assistance Program

• For uninsured or underinsured patients
• Income requirements apply
• May provide medication at no cost
• Phone: 1-877-744-5675

Independent Foundations

• Patient Access Network (PAN) Foundation: 1-866-316-7263
• The Assistance Fund (TAF): 1-855-845-3663
• HealthWell Foundation: 1-800-675-8416
• CancerCare Co-Payment Assistance: 1-866-552-6729
• Patient Advocate Foundation: 1-800-532-5274

Frequently Asked Questions

How is palbociclib different from chemotherapy?

Palbociclib is targeted therapy, not chemotherapy. Chemotherapy kills all rapidly dividing cells (cancer and normal cells like hair, gut lining, bone marrow). Palbociclib specifically targets CDK4/6 proteins that cancer cells need to divide. This gives it a better side effect profile - you won't lose your hair, have severe nausea, or develop neuropathy. However, it does lower blood counts (especially neutrophils), which chemotherapy also does. The key difference: palbociclib targets a specific vulnerability in hormone-positive breast cancer cells.

Why do I need to take a week off every cycle?

The 3-weeks-on, 1-week-off schedule allows your blood counts to recover, particularly neutrophils. Counts typically hit their lowest point around day 15-21, then bounce back during the week off. This scheduled break prevents cumulative toxicity and allows most patients to continue treatment long-term. Don't skip the rest week - it's an essential part of the dosing schedule. Studies specifically tested this schedule and found it balances effectiveness with tolerability.

My white blood count is very low. Should I be worried?

Low white blood count (neutropenia) is expected with palbociclib - it happens in 80-85% of patients. The good news: despite very low counts, serious infections are uncommon (only 1-5%). The neutrophils that remain are functional, and counts recover during your week off. Your doctor monitors this closely and will hold or reduce your dose if needed. What matters most: if you develop a fever (≥100.4°F) when your counts are low, that's an emergency requiring immediate medical attention.

Can I drink alcohol while taking palbociclib?

Moderate alcohol consumption is generally okay, but discuss with your oncologist. There's no direct interaction between palbociclib and alcohol. However, alcohol can worsen some side effects (fatigue, nausea, liver stress) and may affect your immune system when counts are low. If you drink, limit to occasional small amounts. Never drink alcohol if you're taking pain medications or anti-nausea drugs. The more important dietary restriction: absolutely NO grapefruit or grapefruit juice.

Why is grapefruit such a problem?

Grapefruit (and grapefruit juice) contains compounds that block CYP3A enzymes in your gut and liver. Since palbociclib is broken down by CYP3A, grapefruit can increase palbociclib blood levels by 80-90%. This dramatically increases your risk of serious side effects, especially severe neutropenia. The effect lasts 2-3 days, so even occasional grapefruit consumption is risky. Also avoid Seville oranges (used in marmalade) and pomelos. Regular oranges are fine.

I'm premenopausal. Can I still take palbociclib?

Yes, but you must also receive ovarian suppression with goserelin (Zoladex) or leuprolide (Lupron) injections monthly. These drugs temporarily stop your ovaries from producing estrogen, creating a "medically menopausal" state. This is necessary because palbociclib is combined with aromatase inhibitors (which only work when estrogen production is suppressed) or fulvestrant. You'll likely experience menopause-like symptoms (hot flashes, mood changes, vaginal dryness). Discuss fertility preservation before starting if you may want children in the future.

Will I lose my hair?

No, complete hair loss is very rare with palbociclib. About 12-18% of patients experience mild hair thinning, but this is very different from chemotherapy-induced baldness. You won't need a wig or head coverings. Some patients notice their hair becomes slightly thinner or grows more slowly, but most people can't tell you're on treatment. If significant hair loss occurs, talk to your oncologist - it may indicate another issue.

How long will I be on palbociclib?

You'll continue palbociclib as long as it's working and you're tolerating it. This could be months to years - some patients have been on palbociclib for 5+ years. Your oncologist will order scans every 2-3 months to assess if the cancer is responding or stable. If the cancer progresses despite palbociclib, you'll switch to a different treatment (often chemotherapy at that point). If you develop intolerable side effects that don't improve with dose reductions, you may need to stop earlier.

Can palbociclib cure my cancer?

For metastatic (stage IV) breast cancer, palbociclib is not a cure - it's a control strategy. The goal is to keep the cancer stable or shrinking for as long as possible, extending life and maintaining quality of life. In clinical trials, palbociclib extended median progression-free survival by about 10 months compared to hormone therapy alone, and showed overall survival benefit in the PALOMA-3 trial (about 7 months longer). Many patients achieve years of disease control on palbociclib. While not curative, it's a major advance that delays the need for chemotherapy.

What's the difference between palbociclib, ribociclib, and abemaciclib?

All three are CDK4/6 inhibitors that work similarly and have comparable effectiveness. Key differences: (1) Palbociclib causes more neutropenia but less diarrhea; (2) Abemaciclib is taken twice daily continuously (no week off) and causes more diarrhea (60-90%) but less neutropenia - it's also the only one that crosses into the brain, making it preferred if you have brain metastases; (3) Ribociclib can cause QT prolongation (heart rhythm issue) requiring EKG monitoring, but has the strongest overall survival data. Your oncologist will choose based on your specific situation, side effect tolerance, and insurance coverage. All three are excellent options.

I need antibiotics for an infection. What should I tell my doctor?

Always tell any doctor prescribing medications that you're taking palbociclib. Many antibiotics interact with palbociclib. Avoid clarithromycin (strong CYP3A inhibitor) - azithromycin (Z-pack) is a safer alternative. If you need erythromycin or clarithromycin, your palbociclib dose must be reduced to 75 mg. Tell your oncologist before starting any new antibiotic. For simple infections, many common antibiotics are safe (amoxicillin, cephalexin, doxycycline, azithromycin). The same applies to antifungals - avoid ketoconazole and itraconazole if possible.

Key Clinical Trials References

• PALOMA-1: Initial phase 2 trial leading to accelerated FDA approval
• PALOMA-2: Finn RS, et al. N Engl J Med 2016. First-line palbociclib + letrozole vs. letrozole alone
• PALOMA-3: Turner NC, et al. N Engl J Med 2018. Palbociclib + fulvestrant vs. fulvestrant after prior endocrine therapy
• Overall Survival Data: Finn RS, et al. Oncologist 2020 (PALOMA-2); Turner NC, et al. Lancet Oncol 2018 (PALOMA-3)