Phase II trial of panitumumab monotherapy for patients with KRAS exon2 wild type colorectal cancer after progression on cetuximab. HGCSG1101

Background

Both panitumumab and cetuximab known as antibody to EGFR play a key role in treatment with patients for colorectal cancer. Although the action for EGFR is considered to be similar in clinical practice, the differences between these drugs have been reported. The affinity for EGFR shows to be higher in panitumumab. And because of different subclass of antibody between panitumumab [IgG2] and cetuximab [IgG1], it has been reported that cetuximab has Antibody-dependent cellular cytotoxicity (ADCC). Some retrospective analyses have revealed that the administration of panitumumab after cetuximab demonstrate the valuable efficacy, however, the prospective study for cetuximab refractory patients have only been a few reported.

Methods

HGSCG1101 is a multicenter phase II study. Eligibility includes histologically confirmed KRAS exon2 colorectal cancer, previously received oxaliplatin/irinotecan/fluoropyrimidine, and previously refractory for cetuximab. Patients intravenously received panitumumab 6 mg/kg every 14 days. The primary endpoint was 6-month progression-free survival rate (threshold 8%, expected 31%) and the secondary endpoints were safety, response rate, disease control rate, PFS and OS. We estimated that a target sample size of 28 patients.

Results

Between May 2011 and April 2014, 33 pts were enrolled. Two patients were ineligible. Patients characteristics were as follows: median age 67 years (range 44-90), male: female 23:8, PS 0:1:2 17:13:1, best response for cetuximab PR:SD:PD 8:15:5. Median number of panitumumab administration was 4. The median relative dose intensity was 1.000. The main grade 3-4 AE were hypomagnesemia (9.7%) and rash acneiform/pruritus/dry skin (3.2%). 6-month progression-free survival rate was 3.3%. Response rate was 6.5% and disease control rate was 35.5%. Median progression-free survival was 1.9 months (95%C.I. 1.8-1.9 months) and median survival time was 7.8 months (95%C.I. 6.7-8.9 months).

Conclusions

6-month progression-free survival rate as the primary endpoint could not be achieved in this study. We could not demonstrate the efficacy of panitumumab monotherapy for patients in refractory to treatment with cetuximab.

Clinical trial identification

This trial does not have to register, such as the NIH or European equivalent. Hokkaido University Hospital IRB trial number : 010-0313

Legal entity responsible for the study

Specified Nonprofit Corporation : Hokkaido Gastrointestinal Cancer Study Group

Funding

Specified Nonprofit Corporation : Hokkaido Gastrointestinal Cancer Study Group

Disclosure

S. Yuki: Honoraria: Taiho Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eli Lilly Japan Y. Komatsu: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Daiichi Sankyo, Kureha Corporation T. Takahata: Honoraria: Novartis Pharma, Kyowa Hakko Kirin, Janssen Pharmaceutical, Otsuka Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo Y. Sakata: Honoraria: Taiho Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Merck Serono All other authors have declared no conflicts of interest.