Lehigh Valley Topper Cancer Institute to Participate in Pioneering Rectal Cancer Trial

In June 2022, Maged Khalil, MD, with Lehigh Valley Topper Cancer Institute, started receiving calls from patients about a clinical trial for rectal cancer that was headline news.

The results of the 14-person study at Memorial Sloan Kettering Cancer Center (MSK) of an immunotherapy checkpoint inhibitor drug were remarkable. All the participating individuals, who had stage 2 or 3 rectal adenocarcinoma tumors with a specific genetic makeup (deficient DNA mismatch repair protein, or dMMR), had a complete clinical response, with no evidence of tumor on MRI. About 5%–10% of rectal cancers are microsatellite instability-high (MSI-H).

“These results were revolutionary,” Khalil says. “It signaled a paradigm shift in how we might treat rectal cancer.”

Khalil notes that although these tumors are curable, the standard regimen of chemoradiation and surgery can have life-altering effects, including gastrointestinal dysfunction, infertility, sexual dysfunction and more.

To be able to treat a patient with immunotherapy and obviate the need for further treatment is truly exciting,” he says. At the time, Khalil and his colleagues could not offer access to the trial. But this fall, Lehigh Valley Topper Cancer Institute, the only cancer center in the region that is a member of the MSK Cancer Alliance, will be the first site in Pennsylvania to participate in this groundbreaking research.

According to Alexandra Bauman RN, Supervisor, Oncology Clinical Trials Office, the plan is to recruit five people with stage 2 or 3 dMMR tumors and expand from there.

“We hope to coordinate with hematology-oncology physicians and colorectal surgeons who perform standard dMMR/MSI-H testing,” she says. (MSI-H refers to microsatellite instability-high, an equivalent tumor biomarker.)

Individuals will receive intravenous doses of the PD-1 checkpoint inhibitor dostarlimab every three weeks, for up to six months. They will be monitored for tumor response or progression with PET/CT scans, tumor-specific imaging, biopsies and ctDNA (circulating tumor DNA) testing. People who show tumor progression at any point will be treated per standard of care with chemoradiation and/or surgery.

Khalil notes that PD-1 checkpoint inhibitors have been used for many years to successfully treat metastatic cancer, but this is the first time they have been used in a neoadjuvant setting.

“We needed the experience and expertise with these drugs to be able to propose this to patients because they are understandably concerned that their disease might spread while they undergo this experimental therapy,” he says. “It takes a lot of trust for patients to consider this alternative. Fortunately, after the initial results of this trial, we have more evidence that it might be a viable option.”