1161P - Therapeutic outcome of molecular profiling of melanoma patients resistant to standard treatment: Real-world data

Background

Therapeutic options for advanced melanoma patients (pts) resistant to standard treatment (Tx): immunotherapy & anti-BRAF-based targeted therapy represent a high medical need. Objective: Our aim was to evaluate the applicability of precision medicine in melanoma pts who failed standard tx based on molecular profiling (MP) of their tumors & the resulting clinical outcome.

Methods

All pts with advanced melanoma resistant to standard tx who had a MP at Gustave Roussy between April 2021 & March 2023 were included in this retrospective study. MP was performed by using Next Generation sequencing by using Foundation one CDX/liquidCDX & it was based on 3 protocols: STING (NCT04932525), MCLA-128 (NCT03321981) & STARTRK (NCT02568267) which allowed liquid & tissue biopsies studies. Molecular actionability was based on ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) classification.

Results

We performed MP for 184 pts: 174 had melanoma, 2 pts with EWSR1-ATF1 fusion & 1 with EWSR1-CREB1, which allowed a diagnosis correction to clear cell sarcoma & the initiation of the appropriate sarcoma tx, 3 BCC, 3 cSCC & 1 Merkel cell cancer. For the 174 melanoma pts, apart from the BRAF V600 mutation (50% of the pts), a putative actionable molecular orientation was found in 51.6% of the pts. The most frequent molecular alterations were: NRAS (23.2%), PTEN (12.6%), ATM (8.4%), CDKN2A (7.4%), BRAF class II (6.3%), BRAF class III (5.3%), KIT (4.2%) PIK3CA (3.2%), MAP2K1 (3.2%), NF1 (2.1%), AKT (1.1%), HRAS (1.1%), MET (1.1%), ALK (1.1%), ARID1A (1.1%), CDK4 (1.1%), CCND1 (1.1%). Molecularly matched tx was administered to 15 pts: anti-MEK (n = 11) & imatinib (n = 2). Among the 11 pts on anti-MEK, 1 partial response was seen after 9 months of tx & the remaining 10 pts rapidly progressed after 1-3 months of anti-MEK tx as for the 2 pts on imatinib. Unfortunately, no precision medicine tx was available to target the other potentially actionable mutations at the time they were needed.

Conclusions

Potentially actionable mutations can be found in more than 50% of pts with resistant melanoma. Tumor agnostic trials based on molecular alterations should be more broadly available to evaluate the potential benefit of innovative precision medicine in this population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.