For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.
“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.
Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.
Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”
As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.
Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.
Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.
MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.
The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.
Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.
Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.
Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.
This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.
Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.
Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).
To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.
Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.
Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.
A version of this article first appeared on Medscape.com.