ISGIO Conference Explores Enhancing Fellows’ Experience, Ramifications of MSI-High Phenotype

Tabios Bekaii-Saab, MD

As the new chair of the 17th Annual International Society of Gastrointestinal Oncology® (ISGIO) meeting, Tanios Bekaii-Saab, MD, said that this year’s virtual conference will place particular emphasis on fellows’ education and involvement.¹

“We want to preserve the spirit of ISGIO,which ensures that fellows and faculty who are early in their career will understand the evolving landscape of research and standard-of-care therapies in gastrointestinal malignancies,” Bekaii-Saab said during an interview with Targeted Therapies in Oncology prior to the conference. “ISGIO represents a forum in which fellows who are interested in gastrointestinal cancers can present cases, showcase their work, and network with others who can enhance their careers.”

He also emphasized a greater diversifi cation of faculty and presenters who represent multiple institutions. This allows for the largest possible reach and perspective to be presented at ISGIO.

One of the conference’s major advantages over other medical meetings is its timing. ISGIO convenes after the American Association for Cancer Research and European Society of Medical Oncology (ESMO) annual conferences, which occur in the spring and early fall, respectively. In addition, data from the Gastrointestinal Cancers Symposium held in January and the World Congress on Gastrointestinal Cancer in July are covered in detail.

“ISGIO has the advantage of reviewing the newest data from these meetings to provide attendees the latest state-of-the-art advancements, with the objective of helping the community oncologist incorporate them into their daily practices,” said Bekaii-Saab, a professor at the Mayo Clinic College of Medicine and Science and program leader in gastrointestinal cancer at the Mayo Clinic Cancer Center in Phoenix, Arizona.

For the community oncologist whose patient population covers many cancer subtypes, keeping up with approvals and new trial data can be daunting. Incorporating that information into daily practice to benefit patients may be just as challenging. ISGIO gathers the data and its faculty provide perspective on what is applicable and what is transformative in the gastrointestinal setting through lectures, debates, and case studies, Bekaii-Saab said.

Bekaii-Saab anticipates that one of ISGIO’s important presentations will focus on KEYNOTE-177 (NCT02563002), a potentially practice-changing study that compared pembrolizumab (Keytruda) with chemotherapy in patients with newly diagnosed microsatellite instability—high (MSI-H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC).²

An interim analysis of the phase 3 trial that was presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program demonstrated that at a median follow-up of 32.4 months, the median progression-free survival was 16.5 months (95% CI, 5.4-32.4) with pembrolizumab (n = 153) versus 8.2 months (95% CI, 6.1-10.2) with standard chemotherapy with or without bevacizumab (Avastin) or cetuximab (Erbitux; n = 154) in patients with MSI-H/dMMR mCRC. This resulted in a 40% reduction in the risk of disease progression or death (HR, 0.60; 95% CI, 0.45-0.80; P =.0002) (TABLE).²

“In my practice, I began administering pembrolizumab in the first line for patients with MSI-high tumors before the interim analysis for KEYNOTE-177 was announced,” Bekaii-Saab said. “A 40% reduction in risk of disease progression suggests that a patient may never see chemotherapy in their lifetime. That means a better quality of life, and I think that’s quite an achievement.”

Bekaii-Saab suggested that these fi ndings could transform treatment of MSI-high tumors, even beyond mCRC, with far-reaching effects on gastric cancer, pancreatic cancer, and cholangiocarcinoma.

“It does not matter where the cancer is starting; it is the MSI-high phenotype that is essentially determining the level of response, and that is transforming,” Bekaii-Saab said. Although the findings are practice changing, he added, the challenge to elucidate why the other 60% to 70% of patients don’t have as good a response remains.

Other sessions during ISGIO will focus on translational medicine; addressing the emergence of liquid biopsy in gastrointestinal oncology; and the diagnostic, predictive, and prognostic role of circulating tumor DNA in this cancer setting.

Sessions that always spark debate and conversation among conference attendees during ISGIO are the Medical Crossfire® debates. One will cover the question “Should all patients with pancreatic cancer undergo genetic testing?” and the other will address “Which is best for hepatocellular carcinoma, systemic therapy or liver-directed therapy?” Each debate will feature key opinion leaders taking pro and con positions. In pancreatic cancer, Bekaii-Saab suggests that germline and somatic testing be ordered for every patient receiving a diagnosis of this cancer type, which echoes recent National Comprehensive Cancer Network (NCCN) guidelines. The NCCN recommends that all patients with pancreatic cancer undergo germline testing and expanded its recommendations about somatic testing. These guidelines mark a significant change from past recommendations, which listed the tests only as “considerations.”³

“I think it’s important to keep in mind that these genetic test fi ndings have implications not only on targeted agents but, in the case of pancreas cancer, [also help] you understand whether you should choose a platinum- or a taxane-based regimen,” Bekaii-Saab said.

The debates reflect just how far the field of gastrointestinal cancer has come, Bekaii-Saab said. Last year’s plenary session covered BRCA mutations and pancreatic cancer. This year, he expects the MSI-high and colorectal cancer fi ndings to be a major focus of discussion. The emergence of treatable targets is shaking up the gastrointestinal field, suggesting that, as a whole, it is finally catching up with other tumor types as researchers and clinicians begin to put together fi ndings from the past 20 years

“We are starting to understand exactly where these agents fit in the spectrum of care, and that is transforming how we treat our patients,” Bekaii-Saab said. “The great thing is, this is only the tip of the iceberg.”

_References:

_{1. International Society of Gastrointestinal Oncology® Virtual Interactive Conference. Physicians’ Education Resource® (PER®), LLC. Accessed July 21, 2020. https://bit.ly/2CKj8iO}

_{2. Andre T. Shiu KK, Kim TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair defi cient metastatic colorectal cancer: the phase 3 KEYNOTE-177 study. J Clin Oncol.}