29 The Drug Rediscovery Protocol ations to determine clinical benefit). In this cohort, the rate of clinical benefit was 63%. The median progression-free survival was not reached after a median follow-up of 16.5 months. A summary of the clinical benefits to individual patients is presented in Figure 3. The results are consistent with previous reports for immunotherapy in MSI tumours18,19. Overall, nivolumab was tolerated well, and adverse events were largely consistent with those that have previously been reported18,19 (Extended Data Table 5). One patient developed a grade-5 abdominal infection upon intestinal perforation, owing to shrinkage of a peritoneal tumour deposit. One patient experienced grade-5 dyspnoea, possibly attributable to disease progression. Baseline WGS for this cohort was successfully performed in 20 patients (67%) (Table 2). Assessment of MSI on the basis of WGS was highly representative for MSI identification on the basis of immunohistochemistry and PCR. On average, MSI tumours had 866 mutations (range of 614–1,111 mutations) in the genome. Figure 3. Treatment efficacy of nivolumab in completed MSI cohort. Swimmer plot of the time on treatment (in weeks) for each patient (n = 30 patients). Patients marked with an arrow were still on treatment at the point of data cut-off (3 May 2019). The white bars represent the time period for which nivolumab treatment was interrupted (which was optional per protocol after 12 months of treatment) for patients, who still experienced clinical benefit. 2
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