Multidisciplinary molecular tumour board–guided treatment prolongs survival in advanced solid cancers

A multidisciplinary molecular tumour board (MTB) successfully integrates next-generation sequencing (NGS) comprehensive gene profiling (CGP) into real-world clinical practice to guide treatment and significantly extend overall survival (OS) in patients with heavily pretreated advanced solid cancers, a study by researchers from the University of Hong Kong (HKU) has shown.

“Integration of NGS CGP into clinical practice is playing an increasingly important role in oncology,” wrote the researchers. “This multicentre retrospective study investigated the feasibility of the HKU–Hong Kong Sanatorium & Hospital [HKSH] MTB in determining genome-guided therapy for treatment-refractory solid cancers in Hong Kong.” [Lancet Reg Health West Pac 2023;doi:10.1016/j.lanwpc.2023.100775]

MTBs aid frontline oncologists by integrating NGS CGP into clinical practice, thereby facilitating implementation of precision cancer medicine. [Nat Cancer 2022;3:251-261] The main role of MTBs is to enable timely referral of patients to genomically stratified clinical trials. [NPJ Precis Oncol 2022;6:69; JCO Precis Oncol 2023;7:e2200342] However, a majority of studies evaluating MTBs’ clinical impact to date were conducted in Europe or the US. “To our knowledge, this is the first study reported in the region in a Chinese patient population,” noted the researchers.

Patients (n=122; median age, 60 years; male, 52.5 percent; median number of prior treatment lines, 3) whose genetic data were reviewed at the HKU-HKSH MTB between August 2018 and June 2022 were included in the study. The primary endpoints were the proportion of patients who received MTB-guided therapy based on genomic analysis, and OS. Secondary endpoints included the proportion of patients with actionable genomic alterations, objective response rate (ORR), and disease control rate (DCR).

Median OS within the retrospective MTB patient population was 12.2 months. Among patients where MTB recommendations were implemented, median survival was 12.7 months vs 5.2 months in patients who did not proceed with MTB-recommended treatment strategy (hazard ratio, 2.7; 95 percent confidence interval, 1.4–5.1; p=0.0073). The majority (63 percent) of patients were able to adopt MTB treatment recommendations, while 18.9 percent of patients were lost to follow-up and 5.7 percent of patients had not yet exhausted standard-of-care options. The rest of the patients (12.3 percent) who did not receive MTB-recommended treatment usually explained it by financial reasons or personal choice.

In the MTB population, ORR was 28.6 percent and DCR was 65.0 percent. Among responders, median OS was 25.1 months and 1-year OS rate was 81.1 percent. Among patients who achieved disease control, median OS was 32.7 months and 1-year OS rate was 75.4 percent.

The patient population consisted of 12 tumour types, the most common being primary central nervous system (CNS; 18.9 percent), hepato-biliary-pancreatic (HPB; 18.0 percent), and thoracic cancers (16.4 percent). Microsatellite instability was detected in 2.5 percent of cases, while a high tumour mutation burden was detected in 13.9 percent of patients. Germline mutations were confirmed in 4.9 percent of patients.

Of >500 detected genetic alterations, 33 (6.4 percent) were targetable mutations. In the overall patient population, 63.9 percent of patients harboured one or more actionable targets, of which CDKN2A/B, PIK3CA, and SMARCA4 were the most frequently detected (28.2 percent, 14.1 percent, and 10.3 percent, respectively). Tumour types with the highest incidence of actionable targets were primary CNS, thoracic, and HPB cancers (14.8 percent, 12.3 percent, and 12.3 percent, respectively).