Key points are not available for this paper at this time.
e13631 Background: The emergence of novel therapeutic targets, targeted drugs, and immune checkpoint inhibitors has catalyzed a paradigm shift from single-target testing to comprehensive genomic profiling in the treatment of solid tumors. However, the tangible benefits of this shift in terms of treatment optimization and patient prognosis improvement have yet to be fully substantiated. Methods: In this retrospective study, we analyzed genomic data from 1032 patients with solid tumors to identify actionable genetic alterations, calculate tumor mutation burden (TMB), measure PD-L1 expression via immunohistochemistry, and assess microsatellite instability (MSI) status. These assessments were utilized to evaluate potential therapeutic targets and immunotherapy-related markers for each patient. Results: Between January 2018 and July 2020, 1032 patients underwent genomic profiling, received treatment, and were followed up. Of 1156 treatment episodes, 423 involved targeted monotherapy or combination therapy, 114 involved immune checkpoint inhibitor therapy, and 619 involved chemotherapy or anti-angiogenic therapy. Patients receiving matched therapy (n=491) demonstrated significantly higher partial response rates (31.7% vs 10.4%, P<0.001) and longer median progression-free survival (PFS) (159 days vs 96 days, P<0.001) compared to those receiving unmatched therapy (n=665). Based on the highest level of mutation carried, there were 475, 8, 153, 405, and 115 patients with grade I, II, III, IV, and V alterations, respectively. Among patients with grade I-II alterations, 65.63% received targeted therapy, resulting in significantly longer PFS compared to those undergoing immunotherapy or chemotherapy (200 days vs 109 days vs 94 days). Conversely, only 16.8% of patients with grade III-IV alterations received targeted treatment, with marginal PFS improvement (112 days vs 114 days vs 92 days). Notably, an increase in the number of actionable variants was associated with a significant decrease in PFS among patients receiving targeted therapy. However, the number of actionable variants did not significantly affect PFS in patients receiving chemotherapy or immunotherapy. Within our cohort, 44 patients with cancer of unknown primary (CUP) underwent molecular diagnostic evaluation, leading to the reclassification of 32 patients based on their molecular profiles. Notably, 24 patients harbored actionable genetic variants, 9 patients had a high TMB (≥10 Muts/Mb), and 3 patients exhibited high PD-L1 expression (TPS ≥50%). Conclusions: Comprehensive genomic profiling demonstrates clinical utility in guiding treatment decisions and improving prognosis for patients with advanced solid tumors. These findings advocate for the integration of next-generation sequencing into the therapeutic regimens for these malignancies.
Wang et al. (Wed,) studied this question.