Molecular Profiling Can Guide Treatment After Recurrence in Young Cancer Patients

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Molecular profiling at cancer recurrence can guide subsequent therapy in pediatric, adolescent, and young adult patients, according to results of the MAPPYACTS trial published in Cancer Discovery.

Researchers identified at least 1 potentially actionable therapeutic target in 69% of patients. Ten percent of patients had genetic alterations that matched treatments considered “ready for routine use.”  

The objective of the MAPPYACTS trial was to define tumor molecular profiles in young patients with recurrent or refractory cancers and match the patients to the optimal salvage treatment.  


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The study included 774 patients who had tissue collected for sequencing. Their median age was 11.6 years (range, 0.5-38.5 years). The main cancer types were sarcomas (n=290), central nervous system tumors (n=216), other solid tumors (n=181), leukemia (n=54), and lymphoma (n=33).

Sequencing was successful for 632 samples from 624 patients. The researchers identified at least 1 potentially actionable somatic or germline alteration in 432 patients (69%).

Based on these findings, patients received a median of 2 (range, 1-7) recommendations for targeted agents alone or in combination. Treatment recommendations included inhibitors of WEE1 (n=150), mTOR (n=123), CDK4/6 (n=105), MEK (n=95), PARP (n=64), BET (n=59), EZH2 (n=38), FGFR (n=31), and PD-1/PD-L1 (n=31). 

The researchers also found that 10% (44/432) of patients with potentially actionable alterations had recommendations for therapies that were considered ready for routine use. These patients had alterations in genes such as ALK and BRAF

There were 356 patients who had follow-up beyond 12 months, and 30% of them received 1 or more matched targeted therapies. More than half of the therapies (56%) were administered in the context of phase 1/2 trials.

Matched treatment resulted in a 17% objective response rate (ORR) overall. For those patients who received treatments that were ready for routine use, the ORR was 38%. The use of lower-level evidence recommendations resulted in a 14% ORR. 

“Search for high-level evidence gene alterations should now be part of front-line molecular diagnostics and will allow us to introduce active new targeted agents into standard treatment,” the researchers wrote. 

The researchers also found that, among 190 patients with extracerebral tumors, 76% of actionable alterations detected in the tumor tissue were also detected in circulating cell-free DNA (cfDNA). In addition, there were 14 patients who had 35 somatic single-nucleotide variants in cfDNA that were not detected by whole-exome sequencing of tumors. 

“MAPPYACTS has identified future innovative diagnostic and treatment strategies, including the encouraging results of cfDNA analysis in solid extracerebral tumors, which are deserving of validation in further prospective studies,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

ReferenceBerlanga P, Pierron G, Lacroix L, et al. The European MAPPYACTS trial: Precision medicine program in pediatric and adolescent patients with recurrent malignancies. Cancer Discov. 2022;12(5):1266-1281. doi:10.1158/2159-8290.CD-21-1136.



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