Johanna Bendell, MD, director of GI Cancer Research Program, associate director, Drug Development Program, Sarah Cannon Research Institute, discusses a randomized phase III placebo-controlled trial that explored apatinib as a treatment for patients with advanced gastric cancer.

Bendell says apatinib is an oral, VEGFR-2 TKI. During the trial, the drug was studied in Chinese patients as second-line therapy for patients with metastatic gastric cancer. The study found that there was a statistically significant improvement in overall survival in the apatinib arm versus the placebo arm, Bendell says.

The toxicity profile is similar to other VEGFR TKIs but patients in this study also experienced fatigue. Bendell is hopeful that there will be more studies examining the efficacy of apatinib in the United States.

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Dr. Bendell Discusses a Phase III Study of Apatinib in Gastric Cancer

Johanna Bendell, MD, director of GI Cancer Research Program, associate director, Drug Development Program, Sarah Cannon Research Institute, discusses two studies in BRAF-mutated colorectal cancer (CRC).

The studies were both presented at the 2014 ASCO Annual Meeting. The first was an open-label phase I/II study of trametinib, dabrafenib, and panitumumab in combination for patients with 

 mutated CRC. The second was a phase I study exploring the novel agent encorafenib (LGX818) combined with cetuximab with or without BYL719 in patients with advanced 

Bendell says both of these studies showed a response rate of about 35-40%. Usually, patients with 

-mutant CRC treated with single-agent chemotherapy only have a response rate of less than 10%. This study showed that an in-depth understanding of molecularly targeted agents and pathways really makes sense, Bendell says.

View more from the 2014 ASCO Annual Meeting

Johanna Bendell, MD, director of GI Cancer Research Program, associate director, Drug Development Program, Sarah Cannon Research Institute, discusses two studies in BRAF-mutated colorectal cancer.

Dr. Bendell Discusses Two Studies in BRAF-Mutated CRC

Johanna Bendell, MD, director of GI Cancer Research Program, associate director, Drug Development Program, Sarah Cannon Research Institute, discusses the rationale of a 

 looking at onartuzumab (MetMAb) and bevacizumab for patients with metastatic colorectal cancer (mCRC).

The c-MET receptor pathway has been the subject of a lot of recent research, Bendell says. It has been observed that high levels of the c-MET receptor seem to be associated with poor prognosis across multiple tumor types.

A randomized, double-blind, placebo-controlled phase II study will evaluate onartuzumab in combination with bevacizumab plus mFOLFOX-6 in patients with previously untreated mCRC. It is hypothesized that the anti-VEGF abilities of bevacizumab will be synergistic with the anti-MET abilities of onartuzumab.

Johanna Bendell, MD, discusses the rationale of a phase II trial looking at onartuzumab (MetMAb) and bevacizumab for patients with metastatic colorectal cancer (mCRC).

Dr. Bendell on a Study of Onartuzumab Plus Bevacizumab for mCRC

Johanna Bendell, MD, director of GI Cancer Research Program, associate director, Drug Development Program, Sarah Cannon Research Institute, discusses the anti-cancer stem cell antibody OMP-59R5 as a treatment option for patients with metastatic pancreatic cancer.

Bendell says there are many new advances for patients with metastatic pancreatic cancer. At first, there were advances in chemotherapy regimens but the focus has shifted to targeted agents.

At the 2014 Gastrointestinal Cancers Symposium in San Francisco, data was presented on OMP-59R5 in combination with nab-paclitaxel and gemcitabine for patients with untreated metastatic pancreatic cancer. Bendell says this agent targets the stem cells that stay living in pancreatic cancer even after the cancer has been attacked with chemotherapy. These stem cells are important to target as they repopulate cancer cells.

Dr. Bendell on using OMP-59R5 to treat Pancreatic Cancer

Johanna Bendell, MD, Director of GI Cancer Research Program, Associate Director, Drug Development Program, Sarah Cannon Research Institute, discusses the inhibition of heat shock protein 90 (Hsp90) in advanced solid tumors.

Hsp90 is a valuable target for anti-cancer therapies, as it allows for growth factors to live and cancer cells to not undergo apoptosis. Bendell says that by blocking Hsp90, the growth mechanism of action can be stopped and, in combination with cytotoxic chemotherapy, could produce even greater beneficial outcomes.

A phase I study analyzed the Hsp90 inhibitor AUY922 in combination with capecitabine in all patient populations with advanced solid tumors who could see benefit from capecitabine. Among the four patients that saw partial response (pancreatic cancer, breast cancer, and two with colon cancer), two of those patients were previously refractory to fluorouracil. This suggests that Hsp90 inhibition may reverse the effect of chemotherapy resistance. Though the data is preliminary, Bendell views it as a promising outlook.

Dr. Bendell on Hsp90 Inhibition in Advanced Solid Tumors

Johanna Bendell, MD, Director of GI Cancer Research Program, Associate Director, Drug Development Program, Sarah Cannon Research Institute, discusses c-MET inhibition in hepatocellular carcinoma (HCC).

A randomized phase II study compared tivantinib, a c-MET tyrosine kinase inhibitor (TKI), to best supportive care in the second-line setting for patients with advanced HCC. Patients with MET-high HCC saw improvement in progression-free survival and overall survival. There is a need for further exploration of anti-c-MET drugs for this patient population, Bendell says.

A phase I/II study from the 2013 Gastrointestinal Cancers Symposium combined E7050 (golvantinib), a c-MET and VEGFR TKI, with sorafenib, the standard of care for patients with advanced HCC. The phase I portion of the trial has been completed and is now moving on to phase II.

Johanna Bendell, MD, Director of GI Cancer Research Program, Associate Director, Drug Development Program, Sarah Cannon Research Institute, discusses c-MET inhibition in hepatocellular carcinoma.

Johanna Bendell, MD

Articles

Dr. Bendell Discusses a Phase III Study of Apatinib in Gastric Cancer

Dr. Bendell Discusses Two Studies in BRAF-Mutated CRC

Dr. Bendell on a Study of Onartuzumab Plus Bevacizumab for mCRC

Dr. Bendell on using OMP-59R5 to treat Pancreatic Cancer

Dr. Bendell on Hsp90 Inhibition in Advanced Solid Tumors

Dr. Bendell on c-MET Inhibition in Hepatocellular Carcinoma