Predicting clinical benefit from everolimus in patients with advanced solid tumors, the CPCT-03 study

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Identifying predictive biomarkers for targeted cancer therapies is crucial.
• Everolimus, an mTOR inhibitor, shows efficacy but response varies.
• Tumor-agnostic biomarkers could broaden treatment applicability.

Purpose of the Study:

• To identify molecular aberrations predicting response to everolimus, irrespective of tumor type.
• To explore PTEN aberrations as potential biomarkers for mTOR inhibitor sensitivity.

Main Methods:

• Analyzed drug sensitivity and genomic profiles of 835 cell lines to generate hypotheses.
• Conducted a multicenter study on 73 advanced solid tumor patients.
• Performed pre-treatment tumor biopsies for DNA sequencing, copy number profiling, and pS6/pERK activation status.

Main Results:

• Cell line screens identified PTEN as associated with mTOR inhibition sensitivity (P=0.016).
• In patients, PTEN aberrations (copy number loss or mutation) correlated with treatment benefit from everolimus (P=0.046).
• Response and molecular data were available from 43 patients.

Conclusions:

• Loss-of-function aberrations in PTEN may serve as a tumor-agnostic biomarker for everolimus benefit.
• Further confirmation in subsequent studies is warranted.
• PTEN status could guide treatment decisions for patients receiving mTOR inhibitors.