2221P - Precision oncology in advanced thyroid carcinomas: Impact of molecular tests on patients’ outcomes

Background

Standard therapies (ST) for advanced thyroid carcinomas (TC) are heterogeneously available in Europe. In Italy, patients (pts) with 131I-refractory differentiated/poorly differentiated TC (DTC/PDTC) can receive lenvatinib/cabozantinib in 1^st/2^nd line (L), respectively. NTRK/RET/BRAF alterations are mutually exclusive. Targeted therapy (TT) is provided in 1L/2L for NTRK/RET-rearranged TC. BRAF-MEK inhibitors are given in 1L for BRAF-mutant anaplastic TC (ATC), chemotherapy if BRAF wild-type (wt). Immunotherapy (IT) has shown activity in PD-L1 ≥ 1 TC. At our Center, pts not eligible/progressing to ST are studied for actionable molecular targets (AMT). Here we explored the accessibility to novel therapies (NT) and the outcomes of pts who received NT.

Methods

DTC/ATC pts candidate for systemic therapy were tested for BRAF by PCR or DNA Next Generation Sequencing (NGS); if BRAF-wt, FISH or RNA NGS were performed for RET/NTRK fusions. Eligible pts could receive NT (TT/IT) in basket clinical trials (BCT), managed access programs (MAP), off-label (OL). Disease control rate (DCR) and tolerability were annotated. Median progression-free survival (mPFS) from start of NT was estimated with Kaplan-Meier method.

Results

From 2019 to 2022, 116 pts (60% female, median age 69 years, 53% DTC, 20% PDTC, 27% ATC) received at least 1 test; 53% were ST-naïve, 47% pretreated ≥ 1L. Overall, 50 PCR, 39 FISH, 91 NGS DNA, 49 NGS RNA were performed. Histology specimens aged ≥ 5 years led to not-evaluable NGS in 33% vs 6.7% (p = .0002). AMTs were found in 70% pts (median 1/pt, range 0-3), 56.4% received NT (Table). DCR for TT/IT was 97%/86%. 27% pts reported G3 toxicities, 21.6% required TT dose reduction. Table: 2221P

Cases with AMT

Conclusions

A high AMT rate (70%) has been achieved by applying our sequential molecular profiling algorithm. For specimens aged ≥ 5 years PCR should be preferred over NGS DNA to analyze BRAF gene. The majority of pts received NT in MAPs. PD-L1 test/NGS panels including TMB may further expand the therapeutic options.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fondazione IRCCS Istituto Nazionale dei Tumori.

Disclosure

F. Caspani: Financial Interests, Personal, Invited Speaker: Eisai. C. Resteghini: Financial Interests, Personal, Sponsor/Funding: SunPharma. A. Vingiani: Financial Interests, Personal, Sponsor/Funding: Lilly, Roche. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Research Grant: Roche. L.D. Locati: Financial Interests, Personal, Invited Speaker: Eisai, Ipsen, SunPharma, Bayer; Financial Interests, Personal, Advisory Board: MSD, Merck Serono, Eli Lilly, Roche; Financial Interests, Personal, Other, Scientific consultant: Istituto Gentili Srl; Financial Interests, Institutional, Local PI: Eisai; Non-Financial Interests, Leadership Role, Endocrine Tumor Group: EORTC; Non-Financial Interests, Officer, Scientific Chairs Council: EORTC; Non-Financial Interests, Advisory Board: AIOM (Italian Association of Medical Oncology), MSGS (Multidisciplinary Salivary Glands Society); Non-Financial Interests, Advisory Role: AIOCC (Associazione Italiana Oncologia Cervico Cefalica). L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck–Serono, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics e GSK.; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, F. Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck–Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Buran. All other authors have declared no conflicts of interest.