Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board

Abstract

Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. Methods: We retrospectively analyzed all patients referred to our center’s Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel’s target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. Results: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. Conclusion: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.

Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors

“…The literature suggests that only a small fraction of patients, about 10% of sequenced patients, can reach clinical benefits from precision oncology. 21 Nevertheless, this small fraction could be increased as MTB offers new treatment possibilities for the patients, including enrollment in novel clinical trials or consideration of alternative therapies to the SOC. 2 The recommendations derived from an MTB include novel therapeutic approaches, such as off-label therapy and expanded access programs.…”

Does genomic profiling improve clinical outcome in carcinoma of unknown primary? - A systematic review

“…Retrospective analyses of survival data were undertaken in two studies [20,22]. Tumour tissues (FFPE material) of CUP patients were assessed for targetable genomic alterations using large-panel NGS and eligibility for immune-checkpoint inhibitor therapy.…”

“…Tumour tissues (FFPE material) of CUP patients were assessed for targetable genomic alterations using large-panel NGS and eligibility for immune-checkpoint inhibitor therapy. One study [20] found a signi cantly improved PFS in CUP patients who received molecularly guided therapy (n = 30) compared to those who received standard systemic treatment options (n = 17) (4.3 versus 1.9 months; p = 0.0094). In contrast, the other study [22] did not show a signi cant survival bene t in CUP patients treated with molecularly matched therapies as opposed to the standard of care (23.6 versus 14.7 months in OS; hazard ratio 0.568; 95% CI 0.268-1.205; p = 0.13).…”

“…Actionable genomic alterations were investigated in six studies using next-generation sequencing regardless of the primary tumour site (Table 1) [17][18][19][20][21][22]. In addition, ve out of the six studies assessed the effect of immunotherapy on clinical outcome in CUP patients [17,[19][20][21][22].…”

“…PFS versus OS), one of the reasons for the lack of survival bene t may be the relatively small number of CUP patients eligible for targeted treatment (n = 17) compared to the empiric arm (n = 78). One of the reasons for the survival advantage may be the introduction of a Molecular Tumour Board (MTB) [20]. All participants were referred to a MTB which consisted of a panel of experts including medical oncologists, molecular biologists and pathologists, for molecular testing and evaluation of molecular strati ed therapies before commencement of treatment.…”