AVASTIN® (Bevacizumab)

The FDA on January 23, 2013 approved AVASTIN® for use in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy, for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first-line AVASTIN® – containing regimen. The FDA initially approved AVASTIN® in 2004 for the first-line treatment of patients with metastatic carcinoma of the colon and rectum (in combination with intravenous 5-fluorouracil-based chemotherapy). AVASTIN® is a product of Genentech U.S., Inc.

ERBITUX® (Cetuximab)

The FDA on July 9, 2012 granted approval to ERBITUX® for use in combination with FOLFIRI (CAMPTOSAR® [Irinotecan], 5-fluorouracil, leucovorin) for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by FDA-approved tests for this use. ERBITUX® is a product of Eli Lilly and Co.

STIVARGA® (Regorafenib)

The FDA on September 27, 2012 approved STIVARGA® (Regorafenib) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, ELOXATIN® (Oxaliplatin)-, and CAMPTOSAR® (Irinotecan)-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. STIVARGA® tablets are a product of Bayer HealthCare Pharmaceuticals, Inc.

ZALTRAP® (Ziv-aflibercept injection)

The FDA on August 3, 2012 approved ZALTRAP® (Ziv-aflibercept injection), for use in combination with 5-fluorouracil, leucovorin, CAMPTOSAR® (Irinotecan) (FOLFIRI) for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin containing regimen. ZALTRAP® is a product of Sanofi U.S., Inc.

FDA approves STIVARGA® (Regorafenib) for Advanced Colorectal Cancer

SUMMARY: The FDA approved STIVARGA® (Regorafenib), an oral multi-kinase inhibitor for the treatment of patients with metastatic colorectal cancer (CRC) who have progressed on 5FU, ELOXATIN® (Oxaliplatin), CAMPTOSAR® (Irinotecan), anti- VEGF and anti-EGFR therapies. The approval was based on a phase III trial in which 760 patients with metastatic CRC who had progressed after approved standard therapies, were randomly assigned in a 2:1 ratio to receive either STIVARGA® plus best supportive care (BSC) or placebo plus BSC. Patients receiving STIVARGA® had a statistically significant improvement in the overall survival and progression free survival compared to placebo, without any unexpected toxicities. The most common side effects of STIVARGA® were fatigue, loss of appetite, hand-foot syndrome, diarrhea, mucositis, elevated blood pressure, and dysphonia. This important study gives a new option for individuals with advanced colorectal cancer. Grothey A, F. Sobrero AF, Siena S, et al. J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)

Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies

SUMMARY: In this phase III trial, patients with metastatic colorectal carcinoma who had progressed after approved standard therapies were randomly assigned in a 2:1 ratio to receive either Regorafenib, an oral multikinase inhibitor plus best supportive care or placebo plus best supportive care. Seven hundred and sixty patients were randomized. Patients receiving Regorafenib had a statistically significant improvement in the overall survival and progression free survival compared to placebo, without any unexpected toxicities. This important study gives a new option for individuals with advanced colorectal cancer who have progressed on all available standard therapies. Grothey A, F. Sobrero AF, Siena S, et al. J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)

Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT Results of a randomized phase III intergroup study (TML study)

SUMMARY:The ML18147 (TML) is a randomized phase III trial in which patients who received AVASTIN® (Bevacizumab) plus standard chemotherapy as initial treatment (first-line treatment) for their metastatic colorectal cancer were then randomized to either continue AVASTIN® with a different chemotherapy after their cancer progressed (second-line treatment) or receive the different chemotherapy regimen without AVASTIN®. Patient group continuing AVASTIN® as a part of second line treatment demonstrated an improved survival compared to those who received chemotherapy alone, as second line treatment. This study has demonstrated that continuing AVASTIN® with second line chemotherapy post progression, extends survival in patients with metastatic colorectal cancer. Arnold D, Andre T, Bennouna J, et al. J Clin Oncol 30, 2012 (suppl; abstr CRA3503)

ZALTRAP® for second line treatment of metastatic CRC

ZALTRAP® (Aflibercept) is a soluble fusion protein that is capable of binding with high affinity to pro-angiogenic factors such as all VEGF-A isoforms, VEGF-B, and PlGF. This is unlike bevacizumab, which is a monoclonal antibody that only targets all isoforms of VEGF-A.  In the VELOUR trial, second-line chemotherapy in combination with ZALTRAP® (Aflibercept) demonstrated significant improvement in the progression-free survival  as well as overall survival compared to chemotherapy alone. This benefit was seen irrespective of prior bevacizumab therapy. This data was presented at the 13th ESMO world congress.

Regorafenib improves survival in advanced CRC

The CORRECT trial is a randomized phase III  study which demonstrated improved survival with Regorafenib, an oral multikinase inhibitor when compared to placebo, in individuals with advanced colorectal cancer, who had progressed on all available standard therapies. This important study gives a new option for individuals with advanced colorectal cancer. Additional data will be presented at ASCO 2012 meeting.

Intravenous (IV) aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second-line treatment of metastatic colorectal cancer (MCRC) Results of a multinational phase 3 trial (EFC10262-VELOUR)

SUMMARY:ZALTRAP® (Aflibercept) is a soluble fusion protein that is capable of binding with high affinity to pro-angiogenic factors such as all VEGF-A isoforms, VEGF-B, and PlGF. This is unlike bevacizumab, which is a monoclonal antibody that only targets all isoforms of VEGF-A. VELOUR is a phase III trial in which 1,226 patients who had failed oxaliplatin-based therapy received second-line therapy and the comparison was FOLFIRI (leucovorin, fluorouracil, irinotecan) with or without ZALTRAP® (Aflibercept). With a median follow-up of 22.3 months, there was significant improvement in the progression-free survival noted in the ZALTRAP® (Aflibercept) group (6.9 vs 4.67 months; HR = 0.758;P = .00007) as well as overall survival (13.5 vs 12.06 months; HR = 0.817;P = .0032). This benefit was seen irrespective of prior bevacizumab therapy. The authors did point out that in the E3200 Intergroup trial, which tested second-line FOLFOX4 chemotherapy with or without bevacizumab, all of the patients were bevacizumab-naive, whereas 70% in the VELOUR trial were bevacizumab-naive.Van Cutsem E, Tabernero J, Lakomy R, et al.  Results of a multinational phase 3 trial (EFC10262-VELOUR). 13th ESMO World Congress on Gastrointestinal Cancer. Abstract 0-0024.