Abstract 71P
Background
Precision oncology personalizes treatments for cancer patients, aiming to improve their clinical outcomes. ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) allows evidence-based evaluation of genomic findings. Molecular tumor boards (MTBs) multi-disciplinary expertise enables ESCAT implementation and personalized treatment choice.
Methods
We retrospectively reviewed outcomes of patients discussed at European Institute of Oncology MTB between June 2019 and June 2022. We performed descriptive statistics and survival analysis comparing patients that received molecularly-matched treatments (MMT) and non-matched treatments (nMMT).
Results
MTB discussed 251 patients with cancer encompassing 26 different primary cancer types. Breast cancer accounted for 25.5% of the total. 188 (74.6%) patients had at least one actionable alteration. After MTB discussion, 76 patients received MMT while 76 received nMMT. Patients receiving MMT displayed higher overall response rate (37.3% vs 12.9%), median progression-free-survival (PFS 5.8 months, 95% CI 4.1–7.5 vs 3.6 months, 95% CI 2.5–4.8, p=0.041; HR 0.679, 95% CI 0.467–0.987) and median overall-survival (mOS 35.1 months, 95% CI not evaluable vs 8.5 months, 95% CI 3.8 – 13.2; HR 0.431, 95% CI 0.250 – 0.744, p=0.002). Superiority in OS and PFS persisted in multivariable models. Among 61 pretreated patients receiving MMT, 37.5% had superior PFS compared to the prior line (PFS2/PFS1 ratio ≥ 1.3). Higher OS (p=0.001) and PFS (p=0.049) were observed for patients with higher actionability evidence (ESCAT tier I) alterations, while no difference was observed in lower evidence levels. Table: 71P
Most frequent actionable genes
Alteration | Total number | Treated patients | Drug administered | ESCAT at discussion | ORR |
PIK3CA | 51 | 4 | Alpelisib | IA | 1/4 (25%) |
BRCA2 | 32 | 19 | PARP-i | IA | 7/19 (37%) |
BRAF V600 | 20 | 2 | BRAF + MEK-i | IIIA | 1/2 (50%) |
ERBB2 | 17 | 1 | Trastuzumab + pertuzumab | IIIA | 1/1 (100%) |
TMB-HIGH | 16 | 4 | Anti-PD(L)-1 | IC | 2/4 (50%) |
ATM | 15 | 2 | PARP-i | X | 0/2 (0%) |
MSI-HIGH | 14 | 8 | Anti-PD(L)-1 | IC | 4/8 (50%) |
BRCA1 | 11 | 9 | PARP-i | IA | 2/9 (22%) |
RET | 10 | 10 | RET-i | IIIA | 7/10 (70%) |
Conclusions
We report real-world data of the first Italian experience of MTB application in clinical practice. Our work shows that MTBs can yield valuable clinical benefit in terms of OS and PFS. Biomarkers with lower actionability ESCAT level appear to be linked to lower clinical benefit.
Clinical trial identification
This study is approved by IEO Ethical Committee with the reference number UID 3572.
Editorial acknowledgement
None
Legal entity responsible for the study
E. Crimini, M. Repetto.
Funding
Has not received any funding.
Disclosure
E. Guerini-Rocco: Financial Interests, Personal, Advisory Role: AstraZeneca, GSK, Roche, Termo Fisher; Financial Interests, Personal, Advisory Board: Novartis. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. A. Esposito: Financial Interests, Personal, Speaker’s Bureau: Novartis. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council. Patient Advocacy Association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA. All other authors have declared no conflicts of interest.
Resources from the same session
52P - Antitumor efficacy of polypyrrole-polyethyleneimine nanocomplex to target B-cell lymphoma
Presenter: Thi Thuy Nguyen
Session: Cocktail & Poster Display session
Resources:
Abstract
53P - Characterization of the non-ATP competitive PI3Kdelta inhibitor IOA-244 in lymphoma models: From single agent to combination screen and clinical investigation
Presenter: Francesco Bertoni
Session: Cocktail & Poster Display session
Resources:
Abstract
54P - Inhibition of ATM vs ATR in combination with radiotherapy affects cellular toxicity and expression of immune checkpoint molecules differently in HNSCC
Presenter: Tina Jost
Session: Cocktail & Poster Display session
Resources:
Abstract
55P - The SOS inhibitor BAY293 contributes to amplified vertical inhibition of the MAP kinase pathway in human melanoma cells
Presenter: Martin Hohenegger
Session: Cocktail & Poster Display session
Resources:
Abstract
56P - Inhibition of HIF-2α-dependent transcription with small molecule inhibitors may provide therapeutic benefit beyond renal cell carcinoma
Presenter: Kelsey Gauthier
Session: Cocktail & Poster Display session
Resources:
Abstract
57P - Deciphering the role of E2F transcription factor-1 in glutamine metabolism
Presenter: Katharina Huber
Session: Cocktail & Poster Display session
Resources:
Abstract
58P - Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low-expressing breast cancer cells and organoid mode
Presenter: Maryam Arshad
Session: Cocktail & Poster Display session
Resources:
Abstract
59P - The influence of the ABCB1, ABCG2 and OATP1 transporters and the CYP3A enzyme on the bioavailability and tissue distribution of TPX-0131
Presenter: Jamie Rijmers
Session: Cocktail & Poster Display session
Resources:
Abstract
60P - MAPKAP1/SIN1: A promising therapeutic target in resistant BRAF-mutated melanoma
Presenter: Emilien Ezine
Session: Cocktail & Poster Display session
Resources:
Abstract
61P - The cysteine-rich protein 61 (Cyr61) contributes to tumor proliferation and invasion via HGF-mediated NF-kB signaling pathway in human hepatocellular carcinoma
Presenter: Jiyoon Jung
Session: Cocktail & Poster Display session
Resources:
Abstract