Can Immunotherapy Replace Surgery for Stomach Cancer?

A new study conducted in France suggests that immunotherapy could help some patients with stomach cancer avoid surgery.

The phase II clinical trial called GERCOR NEONIPIGA had no comparison group and included only 32 patients, yet after 6 cycles of nivolumab (Opdivo) and ipilimumab (Yervoy) combination immunotherapy, 17 of the 29 patients who underwent surgery (59%) had no signs of a tumor; in other words, a pathological complete response of up to sixty percent!

Indeed, two patients refused surgery after their preoperative endoscopic gastric biopsies showed no tumor cells. Surgery was canceled in a third patient who had previously developed metastasis.

After a median follow-up of 12 months, 30 patients (94%) had no recurrence (return of cancer) or progression (advancement of cancer). The remaining two patients developed metastases before surgery, and one patient died from a cardiovascular complication that developed 3 days after surgery.

If these findings are confirmed by further research, they could represent a major opportunity for patients with stomach cancer who respond to combination immunotherapy. A professor of medical oncology at the Sorbonne University in Paris and the principal investigator, Dr. Thierry Adnre, presenting his findings at the American Society of Clinical Oncology (ASCO) 2022 Gastrointestinal Cancers Symposium, said, "Avoiding surgery is a dream for these patients".

This clinical trial "raises the question of whether surgery can be deferred or avoided in some patients with localized (early-stage) stomach cancer." Given the findings, "treatment without surgery seems possible not for all patients with early-stage stomach cancer, but probably for half, perhaps more." He said that preoperative endoscopic biopsies could be used to identify complete responders followed by active surveillance, as in the two participants who declined surgery.

The study included 16 patients with stomach cancer and 16 with esophagogastric (the esophagus-stomach junction) adenocarcinoma. All of these patients’ tumors had a DNA repair mechanism problem called MSI-H or dMMR, a biological marker we use to predict response to immunotherapy (this genetic condition is present in about 20% of stomach cancers).

At baseline;

• 22 patients had stage T3 stomach cancer (the tumor reaching the serosal membrane surrounding the stomach, but not the abdominal membrane called the peritoneum),
• 4 had stage T2 disease (the tumor reaching the muscle layer of the stomach), and
• the stage could not be assessed by endoscopy in 6 patients.

It was not known whether the cancer had spread to lymph nodes around the stomach, but the patients had no metastases at baseline.

Patients received 6 cycles of nivolumab at 240 mg and 2 cycles of ipilimumab at a dose of 1 mg/kg over 12 weeks, followed by R0 resection (extensive stomach cancer surgery) a median of 5 weeks after the last nivolumab injection.

Results

• Surgical specimens from 17 patients (corresponding to 59% of all patients) showed a complete pathological response to neoadjuvant (preoperative tumor-shrinking) immunotherapy [Becker tumor regression grade (TRD) 1a= ypT0N0]
• 4 patients had less than 10% residual tumor cells in the tumor bed (TRD 1b)

Based on tumor response, 25 patients received 9 additional nivolumab treatments after surgery at monthly doses of 480 mg.

Dr. Andre explained that patients wanted to avoid surgery because of its difficulty and side effects, and that 54% of patients had various complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.

This dual immunotherapy caused side effects similar to those previously reported; 25% of patients had grade 3 or 4 side effects.

The study was conducted at 10 centers in France. About three-quarters of patients were men, and the median age was 65.