American College Of Surgeons - Inspiring Quality: Highest Standards, Better Outcomes

Immunotherapy can improve surgical management and standard of care

OCTOBER 24, 2018
Clinical Congress Daily Highlights, Wednesday First Edition


Immunotherapy has transformed the cancer treatment paradigm, with implications for surgical management. A Wednesday panel session considered the evolving landscape of cancer immunotherapy, and its role in the treatment of viral-associated and other types of cancer.

Recent research has focused on understanding why certain patients respond to immunotherapy while others do not. Biomarkers such as PD-L1 expression or somatic mutation burden have proven useful in certain cancer types to help stratify responders and nonresponders. However, studies suggest that more complex interactions between tumors and their microenvironment may be at play.

Howard L. Kaufman, MD, FACS, chief medical officer, Replimune, Woburn, MA, presented advances in the use of immunotherapy to treat Merkel cell carcinoma (MCC). MCC is a rare, aggressive skin cancer with poor outcomes, and treatment with chemotherapy in stage IV metastatic MCC is seldom durable. MCC is viral-associated, with Merkel cell polyoma virus found in approximately 80 percent of tumors.

Dr. Kaufman presented results from the Phase II JAVELIN trial showing that the immunotherapy avelumab induced therapeutic responses in 32 percent of previously treated MCC patients. Notably, there was no correlation with PD-L1 expression or viral status. However, the data identified two groups of MCC patients who may respond—those with high mutation burden and UV-associated tumors, and those with low mutation burden and viral-associated tumors. This led researchers to hypothesize that the virus itself was mediating the effect of immunotherapy.

“The probable explanation for the response rate in the polyoma virus-positive patients is that the virus itself is contributing to the immune response,” Dr. Kaufman said, suggesting that these findings could inform the treatment of other viral-associated cancers.

Head and neck cancers can be associated with human papillomavirus (HPV). Robert L. Ferris, MD, PhD, FACS, director, University of Pittsburgh (PA) Medical Center Hillman Cancer Center, described the shifting disease landscape showing a decrease in HPV-negative and an increase in HPV-positive head and neck cancers. He noted that these subtypes have different tumor microenvironments, such that the interaction of the virus as well as immune cells plays a role in determining outcomes.

“This is some indication that it’s not just the virus or the carcinogen affecting the tumor cell but there is some interplay with the immune system that differentiates HPV-positive versus HPV-negative tumors,” Dr. Ferris said.

Immunotherapy can also favorably affect the cancer microenvironment, potentially allowing PD-L1-negative tumors to show benefit with immunotherapy. Dr. Ferris underscored the importance of a multidisciplinary approach due to this interaction: “Getting on-treatment biopsies is key, and I think the surgeons need to be part of a multidisciplinary team because otherwise the field won’t understand why not all patients respond.”

Anal carcinoma can also be associated with HPV, and stigma surrounding this cancer has hindered clinical research. Cathy Eng, MD, FACP, Department of Gastrointestinal (GI) Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, described the need for improving clinical guidelines. She highlighted the 2018 update to the National Comprehensive Cancer Network (NCCN) Guidelines for anal carcinoma based on the results of several clinical trials demonstrating the success of nivolumab and pembrolizumab. Dr. Eng presented data from the InterAACT trial, the first randomized Phase II study in treatment-naïve anal carcinoma patients comparing two established chemotherapy regimens. The results of this study could be treatment-changing.

“We believe because this is the first randomized Phase II study that it will create a new standard of care for the NCCN guidelines for treatment naïve, metastatic, surgically unresectable patients,” Dr. Eng said. Ongoing trials are evaluating the use of immunotherapy in these regimens.

In closing, Kenneth K. Tanabe, MD, FACS, chief, Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, highlighted the rapid pace of immunotherapy advancement. It can affect surgical management and enables downstaging for resection. It may replace surgery and change resection of oligometastastic disease, neoadjuvant use, and management of complications. He described several case studies and clinical trials that have demonstrated the ability of immunotherapy to improve surgical outcomes or even reduce the need for surgery. Specifically, he noted that neoadjuvant immunotherapy is now being used even in resectable cases of non-small cell lung cancer.

While recent breakthroughs in immunotherapy have significantly advanced the field, more study into the complex interactions between a tumor and its microenvironment, as well as their impact on surgical management, is needed to improve standard of care.

Additional information

The panel session, New Key to Cancer Cure: Checkpoint Inhibitor Therapy, was held October 24 at the 2018 Clinical Congress of the American College of Surgeons in Boston, MA. Program, webcast and audio information is available online at facs.org/clincon2018.

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