Immune Checkpoint Inhibitors Achieve ‘High Activity’ In MSI-H Tumours

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Microsatellite instability (MSI) status could act as a biomarker for likely response to immune checkpoint inhibitor (ICI) therapy, say the authors of a systematic review and meta-analysis published in JAMA Oncology. 

Fausto Petrelli, from Piazzale Ospedale in Treviglio in Italy, and co-workers suggest this role for mismatch repair (MMR) pathway proteins on finding “high activity” of ICI therapy in patients with advanced high MSI (MSI-H) cancer regardless of tumour type. 

In all, 14 studies of ICI use in MSI-H disease were identified with 939 participants, with prostate, endometrial, pancreas, gastric, ovarian, brain or colorectal cancer, or high-grade glioma. All but two of the studies recruited patients who had received at least one line of therapy for their disease. 

Ten of the trials included in the meta-analysis were phase II, one was a phase III study and another was a pooled analysis of data from two phase I/II trials, while two were prospective or observational studies. 

And the ICIs included in the studies were pembrolizumab, durvalumab, avelumab, and either nivolumab alone or in combination with ipilimumab, the investigators say. 

The primary endpoint of overall response rate (ORR) ranged from 0.0% to 64.7% with a pooled ORR of 41.5%, while data from 13 trials gave a disease control rate of 33.0–81.0% and a pooled value of 62.8%. 

Pooled analysis of seven studies gave a median progression-free survival of 4.3 months, while pooled overall survival (OS) data from five studies gave a median value of 24.0 months. Pooled data on 1- and 2-year rates of OS were 75.6% and 56.5%, respectively, which the authors say is “encouraging” given that “ICIs were mostly offered in advanced lines of therapy”. 

The investigators describe the ORR as being “similar” across tumour histological types, with the highest value at 61.2% for gastric cancer. The lowest ORRs were found for colorectal cancer (47.1%), endometrial cancer (36.1%) and other tumour types (35.5%). 

“Based on these findings, the FDA has released market authorization of pembrolizumab for any solid tumors that have [deficient] MMR/MSI-H and that have progressed following prior therapies and who have no further treatment options”, write Fausto Petrelli and co-authors.

“In addition, it seems appropriate to implement testing for [deficient] MMR/MSI-H patients with any advanced disease who have no more effective systemic therapies available”, they suggest. 

Reference  

Petrelli F, Ghidini M, Ghidini A, Tomasello G. Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers. A systematic review and meta-analysis. JAMA Oncol; Advance online publication 14 May 2020. doi:10.1001/jamaoncol.2020.1046