Hendrik-Tobias Arkenau, MD, PhD, medical director, Sarah Cannon Research Institute UK, discusses the potential of immunotherapy in gastric cancer.

Immunotherapy has shown benefit in some patients with gastric cancer, and 2 agents are currently approved in the third-line setting—nivolumab (Opdivo) and pembrolizumab (Keytruda). However, not all patients benefit, so biomarkers such as PD-L1 are used for proper patient selection. Although it has been shown that patients with higher PD-L1 have better outcomes, Arkenau says there are many patients who are PD-L1—negative who derive benefit from immunotherapy.

In gastrointestinal cancer, tumor mutational burden and microsatellite instability (MSI) are often looked to in addition to PD-L1 as predictors of response to immunotherapy. The approval of pembrolizumab in gastric cancer came from a study of patients with MSI-high tumors. Considering studies like these, as well as what has been seen with PD-L1, Arkenau says that the field needs to focus on biosimilar optimization in order to use immunotherapy effectively.

Videos

Dr. Arkenau on the Potential of Immunotherapy in Gastric Cancer

Hendrik-Tobias Arkenau, MD, PhD, medical director, Sarah Cannon Research Institute UK, discusses survival data with TAS-102 (trifluridine/tipiracil; Lonsurf) in gastric cancer at the 2018 ESMO Congress.

TAGS is a phase III, randomized, double-blind study of TAS-102 versus placebo in patients with refractory metastatic gastric cancer. Arkenau reports that there is an overall survival benefit for TAS-102 plus best supportive care when compared with placebo plus best supportive care. Additionally, progression-free survival was superior with TAS-102 as well. Most of the patients on this study, Arkenau noted, had failed multiple prior lines of treatment before being given TAS-102.

Notably, although patients did not have a higher response rate compared with standard of care with best supportive care, they had better stable disease and disease control rate with TAS-102. This is highly significant, Arkenau says. Quality of life was also improved.

TAS-102 is currently approved for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biologic product, and an anti-EGFR monoclonal antibody, if 

Hendrik-Tobias Arkenau, MD, PhD, medical director, Sarah Cannon Research Institute UK, discusses survival data with TAS-102 (trifluridine/tipiracil; Lonsurf) in gastric cancer at the 2018 ESMO Congress.
 

Dr. Arkenau on Survival Data With TAS-102 in Gastric Cancer

Hendrik-Tobias Arkenau, MD, PhD, founding medical director, executive medical director, Sarah Cannon Research Institute UK, discusses immunotherapy advancements on the horizon in the field of gastric cancer.

Combination regimens, such as PD-1 plus CTLA-4 agents, are currently being explored, Arkenau explains. Recent data that were presented at the 2016 ASCO Annual Meeting demonstrate promise with the management of checkpoint blockade as well as OX40 agonists, which are designed to create co-stimulatory effects on T cells.

Additional data that were presented show intriguing results of a PD-1 and OX40 combination regimen, in that it did not show any additional toxicities nor any drug-to-drug interaction, he adds.

Dr. Arkenau on Advancements on Horizon in Gastric Cancer

Hendrik-Tobias Arkenau, MD, PhD, executive medical director, Drug Development Unit, Sarah Cannon Research Institute-United Kingdom, discusses the overall survival (OS) results of the COMBI-d study, which examined the combination of dabrafenib and trametinib for the treatment of patients with unresectable or metastatic 

The phase III study examined the combination versus single-agent dabrafenib in the first-line setting. Data demonstrated an improvement in OS in the combination arm (25 months) versus the single-agent arm (17 months), Arkenau explains. There was also a 29% reduction in the risk of death.

Patients treated with the combination also had less associated toxicities compared with those treated with the single-agent. These findings suggest that the combination could be the new standard of care for 

Hendrik-Tobias Arkenau, MD, PhD, executive medical director, Drug Development Unit, Sarah Cannon Research Institute-United Kingdom, discusses the overall survival results of the COMBI-d study, which examined the combination of dabrafenib and trametinib for the treatment of patients with unresectable or metastatic BRAF V600-mutated melanoma.


Dr. Arkenau on Dabrafenib Combined With Trametinib for BRAF-mutated Melanoma

Hendrik-Tobias Arkenau, MD, PhD, medical director, Sarah Canon Research Institute, discusses an exploratory analysis of AZD4547 in patients with advanced tumors.

Arkenau says AZD4547, an inhibitor of fibroblast growth factor receptor (FGFR), has demonstrated promise in patients who have FGFR amplification in their tumor. However, the tumor biology is very complicated and other amplifications were found that could inform researchers if AZD4547 is working.

FGFR amplification is rare — only 10-20% of patients with breast cancer, squamous cell lung cancer, and gastric cancer have the amplification.

Of 21 patients dosed with AZD4547, seven had high FGFR and three of these patients (squamous NSCLC, breast, and bladder cancer) had target lesion shrinkage or prolonged (≥24 weeks) disease stabilization. Further work is needed to better understand FGFR signaling, Arkenau says.

Hendrik-Tobias Arkenau, MD, PhD

Articles

Dr. Arkenau on the Potential of Immunotherapy in Gastric Cancer

Dr. Arkenau on Survival Data With TAS-102 in Gastric Cancer

Dr. Arkenau on Advancements on Horizon in Gastric Cancer

Dr. Arkenau on Dabrafenib Combined With Trametinib for BRAF-mutated Melanoma

Dr. Arkenau Discusses AZD4547 and FGFR Amplification in Advanced Solid Tumors