Details

Autor(en) / Beteiligte

• Clark, Amy S
• McAndrew, Nicholas P
• Troxel, Andrea
• Feldman, Michael
• Lal, Priti
• Rosen, Mark
• Burrell, Jessica
• Redlinger, Colleen
• Gallagher, Maryann
• Bradbury, Angela R
• Domchek, Susan M
• Fox, Kevin R
• O'Dwyer, Peter J
• DeMichele, Angela M

Titel

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

Ist Teil von

• Clinical cancer research, 2019-04, Vol.25 (7), p.2072-2079

Ort / Verlag

United States

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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/m 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. 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.