Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer

Clin Cancer Res. 2019 Apr 1;25(7):2072-2079. doi: 10.1158/1078-0432.CCR-18-0790. Epub 2019 Jan 11.


Purpose: The CDK 4/6 inhibitor palbociclib rapidly and reversibly inhibits the cell cycle. The goal of this study was to exploit the cell cycle through intermittent, alternating dosing with palbociclib/paclitaxel to enhance efficacy. We determined the combination dose-limiting toxicity (DLT) in patients with Rb protein-expressing, advanced breast cancer.

Patients and methods: This open-label, phase I trial (NCT01320592) enrolled patients to sequential cohorts of palbociclib orally dosed intermittently between days 1 and 19 of a 28-day cycle alternating with weekly paclitaxel. Dose escalation proceeded in a standard 3 + 3 design. Ten additional patients received the combination at the recommended phase II dose (RP2D). Those who reached response plateau ≥6 cycles could continue on palbociclib alone on a 3 week on/1 week off schedule at one dose level above their combination dose.

Results: Twenty-seven patients enrolled. Although there was only 1 DLT (grade 3 alanine aminotransferase/aspartate aminotransferase at 125 mg), neutropenia (NTP) requiring dose modification in cycle 1 (C1) resulted in an RP2D of 75 mg palbociclib/80 mg/m2 paclitaxel. During C1, the most common adverse event was NTP, occurring in 15 patients (55.6%); grade 1 or 2 nausea and peripheral neuropathy were also observed in 8 patients each (29.6%). The clinical benefit rate was 55% at the RP2D; benefit was observed across all receptor subtypes.

Conclusions: Alternating sequential palbociclib/paclitaxel in patients with Rb+ advanced breast cancer is feasible and safe, without evidence of additive toxicity. This represents a new application for CDK 4/6 inhibitors in Rb+ breast cancer regardless of subtype; efficacy trials are warranted.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / etiology
  • Breast Neoplasms / therapy
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Piperazines / administration & dosage
  • Pyridines / administration & dosage
  • Retreatment
  • Treatment Outcome


  • Piperazines
  • Pyridines
  • palbociclib
  • Paclitaxel

Associated data