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Nivolumab Benefit For MMR-Deficient Patients Extends Past Colorectal Cancer

Patients with advanced mismatch repair-deficient cancers of the prostate, endometrium and other sites may respond to nivolumab therapy
27 Nov 2019
Basic Principles in the Management and Treatment (of cancer);  Endometrial Cancer;  Immunotherapy;  Personalised/Precision Medicine;  Prostate Cancer;  Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: Mismatch repair (MMR) deficiency is associated with response to nivolumab in patients with relapsed or treatment-refractory cancer of the endometrium, prostate and other sites, research shows. 

The US FDA has previously approved pembrolizumab for the treatment of MMR-deficient solid tumours, and nivolumab alone or alongside ipilimumab for patients with MMR-deficient colorectal cancer, but the use of nivolumab for other MMR-deficient solid tumours has “not been explored extensively”, explain Nilofer Azad, from Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, USA, and co-workers. 

Hypothesizing that nivolumab may be active against MMR-deficient cancer at other sites, the team screened 4902 patients with a relapsed or refractory tumours entered into the National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial. 

Overall, 99 patients met the MMR deficiency criteria of complete loss of nuclear expression of MLH1 or MSH2 gene products on immunohistochemistry, 42 of whom were enrolled in the subprotocol Z1D arm of NCI-MATCH, the team reports in the Journal of Clinical Oncology. 

“For this study, we were interested in enrolling patients with MMR deficiency, not in assessing risk for MMR-deficient future cancers. Thus, the prevalence of 2% that we found is likely to be slightly lower than the actual prevalence of MMR deficiencies previously described in noncolorectal solid tumors”, the researchers observe. 

The MMR-deficient patients were aged a median of 60 years and had received a median of three previous treatments before beginning four cycles of nivolumab 3 mg/kg every 2 weeks, followed by 480 mg every 4 weeks. 

The most common tumour histologies were endometrioid endometrial adenocarcinoma (n=13), prostate adenocarcinoma (n=5) and uterine carcinosarcoma/malignant mixed Müllerian tumour (n=4), while there were three cases each of oesophageal/oesophagastric junction adenocarcinoma, cholangiosarcoma, and ductal breast carcinoma. There were 11 other patients with single MMR-deficient tumours of other histologies. 

The objective response rate to nivolumab was 36%, including a complete response in 7% and partial responses in 29%, while a further 21% of the group experienced stable disease. Patients received a median of five cycles of treatment and 21% of patients were continuing with nivolumab at time of analysis. 

Progression-free survival was estimated to be 51.3% at 6 months, falling to 46.2% at 12 months and 31.4% at 18 months. Twenty-two patients died during follow-up and the median overall survival was 17.3 months. 

“Treatment-related adverse events were generally mild and expected”, Nilofer Azad et al comment, with just three grade 4 toxicities and no grade 5 events. Grade 1–3 events most commonly included fatigue (40%), anaemia (33%), rash (17%) and hypoalbuminaemia (17%). 

“The response rate of 36% compares well with the previously reported 31% response rate for nivolumab in MMR-deficient colorectal cancer”, the researchers comment. 

They conclude: “Nivolumab has promising activity in MMR-deficient noncolorectal cancers of a wide variety of histopathologic types.” 

 

Reference  

Azad NS, Gray RJ, Overman MJ, et al. Nivolumab is effective in mismatch repair-deficient noncolorectal cancers: Results from Arm Z1D – a subprotocol of the NCI-Match (EAY131) study. J Clin Oncol; Advance online publication 25 November 2019. DOI: 10.1200/JCO.19.00818

Last update: 27 Nov 2019

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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