NcXHF

MARWAN FAKIH
TABLE 6. EGFR Targeting in Chemotherapy Resistant KRAS-WT mCRC
Karapetis et al 56
NCI-CO17 Study
Price et al 55
ASPECCT Study
Study Design
Randomized phase III clinical
trial
KRAS-WT (exon 2), 230 patients
Randomized phase III noninferiority
clinical trial in
patients with KRAS-WT
1,010 patients
Control
Arm
Experimental
Arm(s) Efficacy Objectives Primary Efficacy Endpoint Other Efficacy Endpoints
BSC Cmab Primary: OS
Secondary: PFS, RR
Cmab Pmab Primary: OS
Secondary: PFS, RR
OS: 9.5 (Cmab) vs. 4.8 months
(BSC) (HR 0.55, p 0.001)
OS: 10.4 (Pmab) vs. 10 months
(Cmab)
Pmab non-inferior to Cmab
PFS: 3.7 (Cmab) vs. 1.9 months
(BSC) (HR 0.40, p 0.001)
RR: 12.8% (Cmab) vs. 0%
(BSC)
PFS: 4.1 (Pmab) vs. 4.4 months
(Cmab) (HR 1.0; 85% CI,
0.88 to 1.14)
RR: 22% (Pmab) vs. 19.8%
(Cmab)
Abbreviations: mCRC, metastatic colorectal cancer; OS, overall survival; RR, response rate; PFS, progression-free survival; HR, hazard ratio; EGFR, epidermal growth factor receptor; Cmab,
cetuximab; Pmab, panitumumab; OR, odds ratio; BSC, best supportive care; WT, wild type.
ance) of all cytotoxic and anti-EGFR therapy. It is important
to note that no randomized data have reported on anti-EGFR
recycling and that the above recommendations in the
second- and third-line treatment with anti-EGFR therapy are
based on clinical trials of patients with anti-EGFR naive disease.
The question of recycling is an important research question
given the RAS-mutation emergence in the setting of
anti-EGFR therapy. It is possible that prolonged breaks after
anti-EGFR progression allow for tumor reconstitution
with anti-EGFR sensitive clones resulting in further benefıt
from anti-EGFR rechallenge. A small phase II clinical trial
supports this concept; however, more studies are needed to
confırm these fındings and to identify the patients who would
best benefıt from this strategy. 57
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: Marwan Fakih, Amgen, Genentech, Sanofi, Sirtex
Medical. Consulting or Advisory Role: Marwan Fakih, Amgen, Sanofi, Sirtex Medical, Taiho Pharmaceutical. Speakers’ Bureau: Marwan Fakih, Amgen, Bayer,
Genentech, Sanofi, Sirtex Medical. Research Funding: Marwan Fakih, Amgen (Inst), Novartis (Inst). Patents, Royalties, or Other Intellectual Property:
None. Expert Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
References
1. Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI
and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;
371:1609-1618.
2. Venook A, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: phase
III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/
leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET)
for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma
of the colon or rectum (MCRC). J Clin Oncol. 2014;32:5s
(suppl; abst LBA4).
3. Allegra CJ, Yothers G, O’Connell MJ, et al. Phase III trial assessing bevacizumab
in stages II and III carcinoma of the colon: results of NSABP
protocol C-08. J Clin Oncol. 2011;29:11-16.
4. Allegra CJ, Yothers G, O’Connell MJ, et al. Bevacizumab in stage
II-III colon cancer: 5-year update of the National Surgical Adjuvant
Breast and Bowel Project C-08 trial. J Clin Oncol. 2013;31:
359-364.
5. Pogue-Geile K, Yothers G, Taniyama Y, et al. Defective mismatch repair
and benefıt from bevacizumab for colon cancer: fındings from NSABP
C-08. J Natl Cancer Inst. 2013;105:989-992.
6. de Gramont A, Van Cutsem E, Schmoll HJ, et al. Bevacizumab plus
oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer
(AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012;
13:1225-1233.
7. Midgley R, Love S, Tomlinson I, et al. Final results from QUASAR2, a
multicentre, international randomised phase III trial of capecitabine
(CAP) /- bevacizumab (BEV) in the adjuvant setting of stage II/III
colorectal cancer (CRC). Paper presented at: ESMO 2014 Congress;
September 2014; Madrid, Spain.
8. Alberts SR, Sargent DJ, Nair S, et al. Effect of oxaliplatin, fluorouracil,
and leucovorin with or without cetuximab on survival among patients
with resected stage III colon cancer: a randomized trial. JAMA. 2012;
307:1383-1393.
9. Taieb J, Tabernero J, Mini E, et al. Oxaliplatin, fluorouracil, and leucovorin
with or without cetuximab in patients with resected stage III colon
cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet
Oncol. 2014;15:862-873.
10. Huang J, Nair SG, Mahoney MR, et al. Comparison of FOLFIRI with or
without cetuximab in patients with resected stage III colon cancer; NC-
CTG (Alliance) intergroup trial N0147. Clin Colorectal Cancer. 2014;13:
100-109.
11. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy
with FOLFOX4 and surgery versus surgery alone for resectable liver me-
e204
2015 ASCO EDUCATIONAL BOOK | asco.org/edbook