Multidisciplinary MTB-guided treatment improves survival outcomes of patients with heavily pretreated advanced solid tumors

28 Jul 2023

A recent study, conducted by the Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong (HKUMed) and the Division of Clinical Pathology & Molecular Pathology, Hong Kong Sanatorium & Hospital (HKSH), has shown that patients with heavily pretreated advanced solid tumors and who had undergone treatment guided by the multidisciplinary molecular tumor board (MTB) exhibited a significantly longer overall survival (OS) than those who were treated with non-MTB-guided therapy.1 The study demonstrated the practicability of next-generation sequencing (NGS) comprehensive genomic profilings (CGPs) in day-to-day clinical settings.1

The advent of NGS CGPs has improved patient outcomes by detecting actionable genetic alterations, enabling genome-guided therapy and personalized approach.1 In 2018, HKUMed and HKSH collaborated to establish a monthly multidisciplinary MTB.1 This initiative aimed to assist frontline oncologists by incorporating NGS CGPs into their clinical practice.1 As NGS testing in Hong Kong is carried out through various commercial platforms, each with their respective testing scope.1 The MTB harmonizes treatment recommendations by thoroughly examining identified genomic alterations using an evidence-based approach.1

A multicenter retrospective study was conducted to assess the impact of the HKU-HKSH MTB-guided therapy on the survival outcomes of patients with heavily pretreated advanced solid tumors.1 Patients who had their NGS CGP reports reviewed at the HKU-HKSH MTB from August 2018 to June 2022 were eligible.1 The primary endpoints were the proportion of patients who underwent MTB-guided therapy and OS.1 The secondary endpoints were the percentage of patients with actionable genomic alterations, objective response rate (ORR), and disease control rate (DCR).1 By the data cutoff on October 31, 2022, the study recruited 122 patients.1 The most common tumor types among these patients were primary central nervous system (CNS), hepato-biliary-pancreatic (HBP), and thoracic cancers.1 The most frequently mutated gene was tumor protein 53 (TP53) (44.3%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) (26.2%), phosphatase and tensin homolog (PTEN) (16.4%), Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.6%), and serine/threonine kinase 11 (STK11) (15.6%).1 A high tumor mutation burden (TMB-H) was detected in 13.9% of patients.1

The results showed that 63% (n=77) of patients in this MTB study adopted the treatment strategies recommended by the HKU-HKSH MTB.1 The primary reasons for not implementing MTB recommendations were either the patient’s personal choice (n=4) or the financial strain of the treatment strategy (n=7).1 Among the MTB population, the 12- and 24- months OS rates were 50.9% and 32.8%, respectively.1 For patients who followed the MTB recommendations, the median OS was significantly higher at 12.7 months, compared with 5.2 months for patients who did not receive the MTB-guided therapy (HR=2.7; 95% CI: 1.4-5.1; p=0.0073).1 Furthermore, patients who followed the MTB recommendations achieved an ORR of 28.6% and a DCR of 65.0%.1 Those who reached ORR or DCR had an OS of 25.1 months (95% CI: 15.6-NR) and 32.7 months (95% CI: 15.8-NR), respectively.1

The HKU-HKSH MTB is the first multicenter pan-cancer precision oncology service predominantly that caters for the Chinese population.1 This study showed a significant improvement in survival outcomes for patients with heavily pretreated advanced solid tumors. 1 The integration of NGS CGPs into the cancer care pathway by implementing a multidisciplinary MTB is therefore advocated.1 Nevertheless, there remains a need for further refinement of the genomic profiling and the MTB platform. 1

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