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Title: Phase IB/II Study of Second-Line Therapy with Panitumumab, Irinotecan, and Everolimus (PIE) in KRAS Wild-Type Metastatic Colorectal Cancer.
Austin Authors: Townsend, Amanda;Tebbutt, Niall;Karapetis, Christos;Cooper, Pamela;Singhal, Nimit;Yeend, Susan;Pirc, Louise;Joshi, Rohit;Hardingham, Jennifer;Price, Timothy
Affiliation: Lyell McEwin Hospital, Adelaide, South Australia, Australia
The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
University of Adelaide, Adelaide, South Australia, Australia
Heidelberg Repatriation Hospital, Austin Health, Heidelberg West, Victoria, Australia
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia
The Royal Adelaide Hospital, Adelaide, South Australia, Australia
Issue Date: 8-May-2018 2018-05-08
Publication information: Clinical Cancer Research 2018; online first: 8 May
Abstract: Background: Inhibition of mTOR in addition to EGFR may overcome resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC). This phase Ib/II study evaluated the safety and efficacy of the combination of irinotecan, panitumumab, and everolimus.Method: Patients with KRAS exon 2 wild-type (WT) mCRC following failure of fluoropyrimidine-based therapy received i.v. irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14-day cycle. The primary endpoint of the phase II study was response rate (RR). Secondary survival outcomes were calculated using the Kaplan-Meier method, and results were analyzed as intention to treat. A preplanned exploratory biomarker analysis was performed.Results: Forty-nine patients were enrolled. Dose level 1 (irinotecan 200 mg/m2, panitumumab 6 mg/kg, and everolimus 5 mg alternate day) was declared the MTD with no dose-limiting toxicities in six patients. Forty patients were treated at dose level 1: median age, 60 years (37-76); 65% male; 45% and 52.5%, respectively, with Eastern Cooperative Oncology Group values of 0/1. Median dose intensity was 85%. Grade 3 toxicities were diarrhea (23%), mucositis (18%), rash (13%), fatigue (8%), dehydration (5%), neutropenia (20%), febrile neutropenia (8%), hypomagnesemia (20%), and hypokalemia (8%). Grade 4 toxicities were hypomagnesemia (5%) and neutropenia (3%). RR was 48%, and stable disease was 43%. Median progression-free survival (PFS) was 5.6 months, and median overall survival (OS) was 10.8 months. Twenty-five patients were RAS/RAF WT and had an RR of 60%, median PFS of 6.4 months, and OS of 11.8 months.Conclusions: The toxicity of the panitumumab, irinotecan, and everolimus regimen is as expected and manageable. The RR of 60% in all RAS/RAF WT supports further study of this combination. Clin Cancer Res; 1-7. ©2018 AACR.
DOI: 10.1158/1078-0432.CCR-17-3590
ORCID: 0000-0001-8277-1199
PubMed URL: 29739790
ISSN: 1078-0432
Type: Journal Article
Appears in Collections:Journal articles

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