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Comprehensive molecular profiling in MOTION study
Olesya A Kuznetsova1, Maxim V Ivanov2, Alexandra A Lebedeva3
1Department of Chemotherapy, Federal State Budgetary Institution (N.N. Blokhin National Medical Research Center of Oncology) of the Ministry of Health of the Russian Federation, Moscow 115478, Russia; OncoAtlas LCC, Moscow 119049, Russia.
Introduction:
Comprehensive molecular profiling (CMP) and molecularly matched therapy (MMT) have uncertain roles in advanced solid tumors. This study evaluates CMP's real-world application in Russia.
Methods:
A retrospective, multicenter study analyzed CMP data from 448 patients with advanced non-hematologic malignancies (2018-2024). Genomic alterations (GA) were classified by ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).
Results:
ESCAT tiers included I (15.4 %), II (4.9 %), III (31.5 %), IV (19.6 %), and V/X (28.6 %). Therapy data were available for 374 patients. MMT was recommended for 56.9 % but implemented in only 23.2 % (MMT group, n = 87). MMT group showed better objective response rate (61.3 % vs. 37.1 %, p = 0.001), disease control rate (24.0 % vs. 9.2 %, p = 0.003), and progression-free survival ratio (PFS 2/1) ≥ 1.3 (45.0 % vs. 16.2 %, p < 0.01) compared to non-MMT group (n = 287). Median overall survival (OS) was borderline improved (12 vs. 8 months, HR 0.74, p = 0.06). Reasons for non-MMT management were low GA targetability (40 %), drug unavailability (30 %), clinical decline (23 %), and clinician preference (7 %). Patients with ≤3 prior therapies, ECOG performance status 0-1, and molecular tumor board discussion saw significant OS gains with MMT even for ESCAT III-V GA (5 vs. 18 months, HR 0.25, p < 0.01).
Conclusion:
MMT following CMP offers clinical benefit for selected patients, even with ESCAT III-V GA, underscoring its potential in personalized oncology.
Insights
Comprehensive molecular profiling (CMP) and molecularly matched therapy (MMT) improve outcomes in advanced solid tumors. MMT showed better response rates and progression-free survival, even for less actionable genomic alterations.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- The role of comprehensive molecular profiling (CMP) and molecularly matched therapy (MMT) in advanced solid tumors remains uncertain.
- This study investigates the real-world application and impact of CMP and MMT in Russia.
Purpose of the Study:
- To evaluate the clinical utility and outcomes associated with CMP and MMT in a Russian cohort of patients with advanced solid tumors.
- To assess the implementation rates and reasons for non-adherence to MMT.
Main Methods:
- A retrospective, multicenter study analyzed CMP data from 448 patients with advanced non-hematologic malignancies.
- Genomic alterations (GA) were classified using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).
- Outcomes were compared between patients receiving MMT and those who did not.
Main Results:
- Molecularly matched therapy (MMT) was recommended for 56.9% of patients but implemented in only 23.2%.
- The MMT group demonstrated significantly higher objective response rates (61.3% vs. 37.1%) and improved progression-free survival compared to the non-MMT group.
- Significant overall survival gains were observed with MMT, particularly for patients with ESCAT III-V genomic alterations, those with limited prior therapies, good performance status, and molecular tumor board discussion.
Conclusions:
- MMT following CMP provides significant clinical benefits for selected patients with advanced solid tumors, including those with ESCAT III-V genomic alterations.
- The findings support the integration of CMP and MMT into routine oncology practice for personalized cancer treatment.
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