Stay tuned for coverage from the 2015 ASCO Annual Meeting. Today, Kumar Abhishek, a SERMO Oncologist shares research about colorectal cancer.
We have not seen much movement in the field of colorectal cancer since the approval of VEGF and EGFR targeted therapies. In today’s oral abstract presentation, there were a few papers which will move the needle forward in the management of colorectal cancer. First of all, lets talk about the brightest star on the horizon under investigation for the treament of a myriad of cancers – immunotherapy. Who knew immunotherapy would be utilized for treatment of colorectal cancer. In a phase II study lead by investigators from John Hopkins looked at immune checkpoint inhibitor in MMR deficient colorectal cancer. Pembrolizumab was administered at 10 mg/kg intravenously every 14 days. Response rates and Disease Control Rates (CR+PR+SD) by RECIST criteria were 40% and 90% in MMR-deficient CRC. Median PFS and overall survival (OS) were not reached in the MMR-deficient CRC group. This study establishes the role of immune checkpoint inhibitor in the treatment of MMR deficienct metastatic colorectal cancer.
The addition Oxaliplatin to 5-FU given concurrently with radiation in the neoadjuvant treatment of stage II and III rectal cancer led to an improved pCR as compared to 5-FU with radiation (Abstract 3500). However the methodological problems with the study makes the results less applicable for clinical practice. The patients were not stratified according to the T-stage, there was imbalance in the two arms of the study and a significant number of patients dropped out of the study before starting treatment and intention-to-treat analysis was not available.
Patients with unresectable liver metastasis benefit from liver directed therapies. SIRFLOX study is an international randomized controlled study designed to assess the efficacy and safety of combining FOLFOX chemotherapy (± bev) with SIRT using yttrium-90 (Y-90) resin microspheres as first-line treatment of pts with liver metastases from mCRC (Abstract 3502). Median follow-up was 36.1 months. In first-line treatment of pts with non-resectable CRC liver metastases, the addition of SIRT to standard chemotherapy failed to improve overall PFS. However, median liver PFS was significantly extended. The addition of SIRT was associated with acceptable toxicity. The OS data will obtained from a combined analysis of three studies – SIRFLOX and two other ongoing studies.
Combining another modality of liver directed therapy – radiofrequency ablation (RFA) improves long term outcome. When RFA was combined with systemic chemotherapy and liver resection in patients with unresectable liver metastasis from colorectal cancer, patient lived longer as compared to when they did not undergo RFA (Abstract 3501). This study was presented by Dr. Ruers on behalf of EORTC (Abstract 3501)
BRAF V600E mutations occur in 5–10% of mCRC and confer a poor prognosis. BRAF and MEK inhibitors by themselves have minimal activity in BRAF mutated mCRC. Combination of EGFR and MAPK targeted therapies have shown a more robust inhibition of BRAF mutant mCRC. Dabrafenib in conjunction with Trametinib and Panitumumab achieved a reponse rate of 26%. Toxicity was manageable with 9% grade 3 diarrhea and 9% grade 3 skin rash. This combination offers a potential therapeutic options for patients who have exhuasted standard therpies.
Kumar Abhishek is a board certified Hematologist-Medical Oncologist. He is employed by a large regional health system in Richmond, VA and works with the multi-specialty medical group. Dr. Abhishek received his medical degree from the University College of Medical Sciences located in Delhi, India, and completed his internal medicine residency from Carilion Clinic in Roanoke, Va. He also finished a fellowship in hematology and medical oncology from Saint Louis University in St. Louis, MO. Before starting his training in hematology and oncology, he worked as a clinical instructor and hospitalist at Allegheny General Hospital in Pittsburgh, Pa., and Chippenham Johnston-Willis Hospital in Richmond, Va.