Avelumab maintenance in gastric cancer is down but maybe not out

A ‘yin-yang’ pattern of survival

“Monotherapy checkpoint blockade with anti–programmed death-1 (PD-1) and anti–PD-L1 inhibitors has had relatively unimpressive results in gastroesophageal adenocarcinoma as a whole,” said invited discussant Daniel V. T. Catenacci, MD, of University of Chicago Medicine.

He added that the JAVELIN Gastric 100 survival analysis was noteworthy for the presence of a “yin-yang” pattern, whereby the avelumab curve during follow-up was lower than the chemotherapy curve initially but came out on top eventually.

The 12-month overall survival rate was 43.6% with avelumab and 45.3% with chemotherapy. The 24-month overall survival rates were 22.1% and 15.5%, respectively.

This type of pattern is seen in many similar gastroesophageal adenocarcinoma trials of checkpoint inhibitor monotherapy, even among patients selected for higher CPS, Dr. Catenacci noted.

“This tells us that standard chemotherapy is better in a large subgroup of patients and worse in a separate subgroup: those with MSI-high [microsatellite instability–high], and then MSS [microsatellite stable] with even higher PD-L1 scores like CPS greater than 50, low burden of disease (few metastatic sites), preserved performance status, EBV [Epstein-Barr virus] positivity, Asians within global studies compared with non-Asians, and other unknown factors,” Dr. Catenacci explained.

He commended the design of the JAVELIN Gastric 100 trial, whereby the 38% of patients having rapidly progressive disease were excluded, as this subset is known to fare poorly on checkpoint inhibitor monotherapy.

“This could be potentially a great way to select for those patients most likely to benefit,” Dr. Catenacci said. “Unfortunately, even despite that large fallout, the yin-yang curve was still observed in the intention-to-treat population (unselected by any biomarker). This tells us that, even among the most stable and best prognostic patients, checkpoint blockade is still inferior to standard chemotherapy in a large subgroup of patients.”

However, among patients with a CPS of at least 1, the overall survival curve was consistently higher with avelumab.

“So perhaps by excluding patients with rapid disease progression (about 40% of patients) and then those that are CPS 0 (about 33% more of the total), you can then safely switch to monotherapy checkpoint blockade to first do no harm, and also to do better than standard chemotherapy,” Dr. Catenacci proposed.

“However, we have to be careful, as this was an unplanned retrospective analysis and so should be confirmed prospectively. We might also argue that a higher CPS cut off of greater than or equal to 10 could enrich for the benefit observed. Future ongoing phase 3 studies may help to further increase our understanding of where and where not to implement checkpoint monotherapy or combination therapy with standard chemotherapy.”

The JAVELIN Gastric 100 trial was sponsored by EMD Serono and Merck KGaA, which market avelumab in collaboration with Pfizer. Dr. Moehler disclosed relationships with these companies and many others. Dr. Catenacci disclosed relationships with Merck and other companies.

The 2020 GI Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

SOURCE: Moehler MH et al. 2020 GI Cancers Symposium, Abstract 278.