Relationship Between Clinicopathological Features and Immunotherapy Benefit Among Patients With dMMR/MSI-High Metastatic or Unresectable Gastric Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Giovanni Randon, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, presented results from an international cohort study relating clinicopathological features and immunotherapy benefit among patients with dMMR/MSI-high metastatic or unresectable gastric cancer treated with anti-PD-1-based therapies.

Dr Randon concluded, “anti-PD-1 based therapies have a significant activity and efficacy in patient with microsatellite instability, high metastatic gastric cancer, worse ECOG performance status, non-resected primary tumor, presence of bone metastasis and ascites are associated with inferior outcomes upon exposure to anti-PD-1 based therapies.”

Transcript:

Good evening. I am Giovanni Randon. I'm a medical oncologist at the National Cancer Institute in Milano, Italy, and I work on gastrointestinal malignancies. Today I presented a work on patients with microsatellite instability, high metastatic gastric cancer. Microsatellite instability is rare in advanced gastric cancer, and no more than five percent of them present to this condition. As you know, microsatellite instability is the strongest predictive biomarker for immunotherapy benefit. However, due to the rarity of this condition, no randomized clinical trials have been conducted specifically in this biomarker selected population.

The objectives of our work were to identify clinical predictive factors of immunotherapy benefit in this specific population. To this heme we enrolled patients with metastatic gastric cancer treated with anti-PD-1 based therapies at 9 institutions globally. In our dataset, we included 130 patients. Most of them were treated with anti-PD-1 monotherapy, but only 25% of them received upfront immunotherapy. Since we performed real-world work, we included patients that are usually excluded from clinical trials, such as those with older age, ECOG performance status of 2, bone metastasis, and ascites.

In our work, the objective response rate of anti-PD-1 based therapy was 66%, and with a 2-year follow-up, the 2-year PFS rate was 56% and the 2-year OS rate ranged up to 63%. In the multi-variable analysis worse ECOG performance status, presence of bone metastasis, peritoneal metastasis associated with ascites and non-resected primary tumor were significantly associated with worse outcomes.

We chose to develop a prognostic score in order to better classify patients that are candidates for receiving anti-PD-1 blockade. We identified 3 prognostic categories using the hazard ratios logs of the variables significantly associated with OS in the multi-variable model. These categories allowed to better stratify both PFSs and OS compared to the single variables. Almost all patients with poor risk disease, experienced a disease progression or death within one year.

In conclusion, anti-PD-1 based therapies have a significant activity and efficacy in patient with microsatellite instability, high metastatic gastric cancer, worse ECOG performance status, non-resected primary tumor, presence of bone metastasis and ascites are associated with inferior outcomes upon exposure to anti-PD-1 based therapies. We identified three prognostic categories such as poor, intermediate, and good risk.

While patients with good risk may benefit from anti-PD-1 monotherapy, patient with intermediate to poor risk may be better candidates for a combination of anti-PD-1 with chemotherapy or an anti-CTLA-4 agent or should be evaluated for inclusion in clinical trials with novel immune checkpoint inhibitors. However, the predictive impact of this prognostic classification should be validated by randomized clinical trials. Thank you all for your attention.

Source:

Randon G, Aoki Y, Cohen R, et al. Outcomes and a prognostic classifier in 130 patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-13