537P - A phase IB/II study of second-line therapy with panitumumab, irinotecan and everolimus (PIE) in metastatic colorectal cancer (mCRC) with KRAS wild...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Amanda Townsend
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Townsend1, N. Tebbutt2, C.S. Karapetis3, P. Cooper4, N. Singhal5, S. Yeend6, L. Pirc4, T.J. Price1
  • 1Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, 5011 - Adelaide/AU
  • 2Medical Oncology, Austin Hospital, AU-3084 - Heidelberg/AU
  • 3Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide/AU
  • 4Medical Oncology, The Queen Elizabeth Hospital, 5011 - Adelaide/AU
  • 5Medical Oncology, Royal Adelaide Hospital RAH Cancer Centre, Adelaide/AU
  • 6Medical Oncology, The Queen Elizabeth Hospital, Adelaide/AU

Abstract

Aim

The mammalian target of rapamycin (mTOR) is a key downstream protein activated via PI3K-AKT pathway, and regulates cell growth, proliferation, and survival. Inhibition of mTOR in addition to EGFR may overcome upstream resistance to EGFR inhibitors in CRC. The phase Ib study of the maximum tolerated dose of this combination has previously been reported. This is the interim safety analysis of the phase II study.

Methods

Patients with KRAS exon 2 WT mCRC following failure of first line fluoropyrimidine based therapy received IV irinotecan (200mg/m2) and panitumumab (6mg/kg) every 2 weeks, and everolimus 5mg orally alternate days throughout a 14 day cycle. The primary endpoint was response rate and secondary endpoints were safety and toxicity, progression free survival and overall survival. Survival outcomes were calculated using Kaplan-Meier method.

Results

27 patients have been treated at the MTD. Median age 60 yrs (41-81), M/F 16/11, ECOG 0/1 13/14. 3 patients were not evaluable for response. Safety data is presented on all 27 patients and efficacy data on 24 evaluable patients. The median number of cycles of the PIE combination received was 4.5 (range 1-28 cycles) with 7 patients still on treatment. Grade 3 toxicities were mucositis (7%), fatigue (7%), diarrhoea (26%), rash (19%), hypomagnesemia (22%), neutropenia (33%), febrile neutropenia (7%), and anaemia (11%). The only grade 4 toxicity was hypomagnesemia (4%). The response rate was 33% and stable disease 50% with disease control of 83%. The median progression free survival was 6.7 months. These efficacy results surpass the early stopping rules for this study and support continuation.

Conclusions

This regimen has an acceptable safety profile with common toxicities of diarrhoea and rash. Early efficacy results support ongoing study of this combination. Extended RAS and PI3K testing will be performed on this study population.

Disclosure

N. Tebbutt: Amgen advisory board; C.S. Karapetis: Amgen advisory board; T.J. Price: Advisory board for Amgen, Novartis and Merck. All other authors have declared no conflicts of interest.