Last updated: June 24, 2026
Ibrance (palbociclib, PD-0332991) is an oral, first-in-class CDK4/6 inhibitor developed by Pfizer. It was the first CDK4/6 inhibitor approved by the FDA (February 2015 accelerated approval; March 2017 regular full approval) and remains the most prescribed CDK4/6 inhibitor in HR+/HER2- advanced breast cancer worldwide. Always combined with endocrine therapy (an aromatase inhibitor in first-line; fulvestrant in second-line). Dosed 125 mg daily on a 21-days-on / 7-days-off schedule.
Mechanism of action:Palbociclib inhibits cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), two kinases that — in complex with cyclin D — phosphorylate the retinoblastoma (Rb) tumor-suppressor protein and drive cells from G1 phase into S phase of the cell cycle. In HR+/HER2- breast cancer, estrogen-receptor signaling drives cyclin D1 expression and locks the cell into CDK4/6 dependence. Inhibiting CDK4/6 keeps Rb in its active, hypophosphorylated state, blocking the G1/S transition and arresting tumor-cell proliferation. See the CDK4/6 inhibitor mechanism hub for the broader class context.
Regulatory status:FDA-approved in HR+/HER2- advanced breast cancer across 3 settings: 1L + aromatase inhibitor (PALOMA-1 accelerated Feb 2015 / PALOMA-2 full Mar 2017), 2L+ + fulvestrant post-endocrine progression (PALOMA-3 Feb 2016), and male HR+/HER2- breast cancer (Apr 2019). NOT FDA-approved for adjuvant early-stage breast cancer — both PALLAS (NCT02513394) and PENELOPE-B Phase 3 adjuvant trials failed their primary endpoints. This contrasts with Kisqali (ribociclib, NATALEE Sep 2024) and Verzenio (abemaciclib, monarchE Oct 2021), which are approved adjuvant.
HR+/HER2- breast cancer is the most common form of breast cancer worldwide. It is driven by the female hormone estrogen, which binds the estrogen receptor inside breast cancer cells and turns on a growth program. A core part of that growth program is a protein called cyclin D1, which partners with two kinases — CDK4 and CDK6 — to push cells out of a resting state and into cell division.
Normal cells have a tumor-suppressor protein called Rb (retinoblastoma) that acts as a brake on cell division. CDK4 and CDK6 release this brake by adding phosphate groups onto Rb (a process called phosphorylation). In HR+/HER2- breast cancer, the estrogen-driven growth program keeps CDK4/6 active, Rb braked off, and cells dividing.
Ibrance blocks CDK4 and CDK6 directly. With those two kinases turned off, Rb stays in its active "brake-on" state, the cancer cells stop dividing, and combining Ibrance with an aromatase inhibitor (which lowers estrogen) or with fulvestrant (which degrades the estrogen receptor) attacks the disease on two fronts at once. This is why Ibrance is always given in combination with endocrine therapy — never alone — in HR+/HER2- advanced breast cancer.
The biggest practical limitation: Ibrance is approved only in advanced or metastatic breast cancer. Despite enrolling more than 5,000 patients across two large Phase 3 trials (PALLAS and PENELOPE-B), Ibrance did not improve outcomes in the adjuvant (early-stage) setting. Patients evaluating CDK4/6 inhibitors for early-stage disease should know that only Kisqali and Verzenio are FDA-approved adjuvant options.
Ibrance has accumulated 3 FDA approvals since the February 2015 first-in-class accelerated approval, all in HR+/HER2- advanced breast cancer. The pivotal trial, FDA decision date, and biomarker setting are listed for each.
1L combination with letrozole (or another aromatase inhibitor), postmenopausal HR+/HER2- advanced breast cancer
2L+ combination with fulvestrant after progression on prior endocrine therapy, HR+/HER2- advanced breast cancer
Male HR+/HER2- advanced or metastatic breast cancer
⚠ What Ibrance is NOT approved for: adjuvant early-stage breast cancer
Ibrance is NOT FDA-approved for adjuvant (early-stage, curative-intent) treatment of HR+/HER2- breast cancer. Two large Phase 3 adjuvant trials both failed their primary endpoints:
By contrast, Kisqali (ribociclib) is FDA-approved adjuvant in HR+/HER2- node-positive high-risk early breast cancer based on the NATALEE trial (FDA Sep 2024), and Verzenio (abemaciclib) is FDA-approved adjuvant based on the monarchE trial (FDA Oct 2021 — the first adjuvant CDK4/6 inhibitor). Patients evaluating CDK4/6 inhibitors for early-stage curative-intent treatment should know that only Kisqali and Verzenio are FDA-approved adjuvant options. See the CDK4/6 inhibitor mechanism hub for the cross-drug comparison.
Curated highlights from 33 recruiting interventional Ibrance (palbociclib) trials in the ClinTrialFinder corpus as of June 24, 2026. Trials are grouped by indication and ordered roughly by phase and clinical significance.
This is where palbociclib was born (FDA Feb 2015) and where the deepest trial pool sits. Active themes: high-dose / autophagy-targeting combinations, next-generation CDK4/6i comparisons, post-progression sequencing, premenopausal optimization, and predictive biomarkers.
CDKN2A (p16) loss is a molecular biomarker for CDK4/6 dependence in non-breast cancers. HPV-unrelated HNSCC has frequent CDKN2A loss, making it a rational CDK4/6 inhibitor target.
Well-differentiated and dedifferentiated liposarcoma harbor frequent CDK4 amplification on chromosome 12q (alongside MDM2) — one of the strongest non-breast biomarker rationales for CDK4/6 inhibition.
Showing curated highlights from 33 recruiting Ibrance (palbociclib) interventional trials in the ClinTrialFinder corpus as of June 24, 2026. For the latest list: view all recruiting palbociclib trials on ClinicalTrials.gov.
Targets: CDK4 and CDK6 (cyclin-dependent kinases 4 and 6) — the two kinases that pair with D-type cyclins to drive the G1-to-S phase transition of the cell cycle.
Mechanism: In HR+/HER2- breast cancer, estrogen-receptor signaling drives cyclin D1 expression. Cyclin D1 binds CDK4 / CDK6 and the active complex phosphorylates the retinoblastoma (Rb) tumor-suppressor protein. Phosphorylated Rb releases the E2F family of transcription factors, which turn on S-phase genes and drive cell division. Palbociclib binds the ATP pocket of CDK4 and CDK6, blocking their kinase activity. With CDK4/6 inhibited, Rb stays hypophosphorylated and active, E2F stays sequestered, and the cell arrests in G1. The combination with endocrine therapy (which lowers estrogen or degrades the estrogen receptor) attacks the same growth program at two different points — upstream and downstream of cyclin D1.
Class context: Palbociclib was the first FDA-approved CDK4/6 inhibitor (Feb 2015). Three other CDK4/6 inhibitors are FDA-approved — ribociclib (Kisqali, Novartis, Mar 2017 metastatic + Sep 2024 NATALEE adjuvant), abemaciclib (Verzenio, Eli Lilly, Sep 2017 metastatic + Oct 2021 monarchE adjuvant, the first adjuvant CDK4/6i), and trilaciclib (Cosela, G1 Therapeutics, Feb 2021 for myelopreservation in SCLC chemotherapy — a distinct mechanism). Next-generation CDK4-selective agents (PF-07220060, BGB-43395) aim to spare CDK6-mediated hematologic toxicity. See the CDK4/6 inhibitor mechanism hub for the cross-drug comparison.
What is Ibrance (palbociclib)?
Ibrance is the brand name for palbociclib (PD-0332991), an oral, small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) developed by Pfizer. It was the first CDK4/6 inhibitor approved by the FDA (February 2015 accelerated approval; March 2017 regular full approval), based on the PALOMA-1 and PALOMA-2 trials in HR+/HER2- advanced breast cancer. Palbociclib works by blocking CDK4 and CDK6, two kinases that — together with cyclin D — phosphorylate the retinoblastoma (Rb) tumor-suppressor protein and drive cells from G1 phase into S phase of the cell cycle. In HR+/HER2- breast cancer, estrogen-receptor signaling drives cyclin D1 expression; CDK4/6 inhibition collapses this growth program. Ibrance is taken by mouth (125 mg daily) on a 21-days-on / 7-days-off schedule and is always combined with endocrine therapy (an aromatase inhibitor or fulvestrant) — never as monotherapy.
Which breast cancer patients is Ibrance FDA-approved for?
Ibrance is FDA-approved in HR+/HER2- advanced or metastatic breast cancer in three settings. First-line (PALOMA-1 / PALOMA-2): palbociclib + letrozole (or another aromatase inhibitor) for postmenopausal women — initial accelerated approval Feb 2015 (PALOMA-1), converted to regular full approval Mar 2017 based on PALOMA-2 PFS. Second-line and beyond (PALOMA-3): palbociclib + fulvestrant for patients whose disease has progressed on prior endocrine therapy — FDA Feb 2016. Male breast cancer: Apr 2019 approval for men with HR+/HER2- advanced or metastatic breast cancer, based on real-world evidence plus a male subset of PALOMA-3. Across all settings, the patient must have HR-positive (ER+ and/or PR+) and HER2-negative disease. Ibrance is NOT FDA-approved for adjuvant (early-stage curative-intent) breast cancer — see the dedicated FAQ below.
What is the difference between Ibrance, Kisqali, and Verzenio?
All three are oral CDK4/6 inhibitors approved for HR+/HER2- metastatic breast cancer, with overlapping but distinct profiles. Dosing schedule: Ibrance (palbociclib) and Kisqali (ribociclib) are dosed 21-days-on / 7-days-off; Verzenio (abemaciclib) is continuous (no break), reflecting its higher CDK4-vs-CDK6 selectivity and lower hematologic toxicity. Adverse-event profile: Ibrance's dominant toxicity is neutropenia (often Grade 3-4 but rarely febrile); Kisqali adds a QTc-prolongation signal (ECG monitoring required) and hepatic-function monitoring; Verzenio's dominant toxicity is diarrhea and venous thromboembolism, with less neutropenia. Adjuvant approval: only Verzenio (FDA Oct 2021, monarchE) and Kisqali (FDA Sep 2024, NATALEE) are FDA-approved in the adjuvant high-risk early breast cancer setting — Ibrance failed its adjuvant Phase 3 trials (PALLAS and PENELOPE-B). For 1L metastatic HR+/HER2-, all three are appropriate choices in combination with an aromatase inhibitor; tolerability and AE preference often guide selection.
What are the main side effects of Ibrance?
The most common side effect is neutropenia (low neutrophil count) — reported in ~80% of patients all-grade, with Grade 3-4 neutropenia in ~65% in the PALOMA trials. Unlike chemotherapy-induced neutropenia, palbociclib-induced neutropenia is mechanism-based (CDK6 inhibition in hematopoietic progenitors), rapidly reversible during the 7-day off-week, and febrile neutropenia is uncommon. Routine complete blood count monitoring is required at baseline, every 2 weeks for the first 2 cycles, then on day 1 of each subsequent cycle, with dose interruption / reduction for Grade 3-4 events. Other common side effects: fatigue, anemia, thrombocytopenia, alopecia (hair thinning), nausea, diarrhea, stomatitis, decreased appetite. Unlike Kisqali, palbociclib does not cause clinically significant QTc prolongation. Drug-drug interactions: palbociclib is a CYP3A4 substrate — strong CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit juice) can increase exposure, and strong CYP3A4 inducers (rifampin, St. John's Wort) can decrease it. Review concomitant medications with your oncology team.
Is Ibrance approved for adjuvant early-stage breast cancer?
No. Ibrance (palbociclib) is NOT FDA-approved for adjuvant treatment of early-stage breast cancer. Two Phase 3 adjuvant trials both failed to meet their primary endpoints: PALLAS (NCT02513394, ~5,800 patients, 2 years of palbociclib + endocrine therapy vs endocrine therapy alone in stage II-III HR+/HER2- breast cancer) did not improve invasive disease-free survival; PENELOPE-B (~1,250 high-risk residual-disease patients post-neoadjuvant chemotherapy) also missed its primary endpoint. This contrasts sharply with the two other CDK4/6 inhibitors in the class: Kisqali (ribociclib) is FDA-approved adjuvant in HR+/HER2- node-positive high-risk early breast cancer based on the NATALEE trial (FDA Sep 2024), and Verzenio (abemaciclib) is FDA-approved adjuvant based on the monarchE trial (FDA Oct 2021 — the first adjuvant CDK4/6 inhibitor). The mechanistic explanation for the divergence remains debated — possible factors include differences in CDK6 inhibition (palbociclib > ribociclib > abemaciclib for hematologic toxicity), continuous vs intermittent dosing (Verzenio is continuous; Ibrance and Kisqali are 21-on / 7-off; the chemo-like 7-day micro-environment recovery may matter in adjuvant), and differences in trial population enrichment for high-risk disease (monarchE and NATALEE enrolled more enriched high-risk populations than PALLAS). For patients deciding between CDK4/6 inhibitors in the adjuvant setting, only Kisqali and Verzenio are FDA-approved options.
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