Molecular Screening of Advanced Refractory Cancer Patients

Routine Molecular Screening of Advanced Refractory Cancer Patients
An analysis of the ProfilER-01 study presented at ASCO 2017

Date: 09 Jun 2017
Topic: Personalised medicine

During Clinical Science Symposium entitled “Translating Tumor Sequencing Into Clinical Decision-Making: The Record to Date” held on 3 June at ASCO 2017 Annual Meeting in Chicago, US, the investigators from the Centre Léon Bérard in Lyon, France presented the results of a molecular analysis of the patients included in the ProfilER-01 study, one of the largest trial assessing high-throughput genomic analyses for large varieties of cancer. The findings show that routine genomic testing is feasible in a local and regional setting. They found that screening of heavily pretreated advanced cancer patients limits the number of patients who can actually receive molecular targeted therapy, but patients who could receive recommended molecular targeted agent have a better overall survival than those who did not.

ProfilER (NCT01774409) is a prospective molecular profiling clinical trial exploring cancer cell genomic alterations in patients with advanced disease to guide targeted treatment. Patients with confirmed diagnosis of advanced cancers are eligible. DNA extracted from either archival or fresh collected tumour samples was analyzed by targeted exon sequencing of cancer related genes and whole genome array comparative genomic hybridization (CGH). A multidisciplinary molecular board, consisting from a panel of clinicians and scientists, analyzed genomic data and recommended molecular targeted therapies when actionable alterations are found.

In total 2676 patients were enrolled (of whom 316 ongoing); 1944 with tumour genomic profiles; 1004 (52%) with at least one actionable mutation. Sex ratio was 45%:55% (male:female). Median age range was 59 years.

Among patients with actionable alterations affected tumour types were breast cancer, gynaecological cancers, head and neck cancer, lung cancer, sarcoma, CNS malignancies, colorectal cancer, liver, pancreatic and biliary tract cancers.

Mutations (including substitutions and small indels), amplifications and homozygous deletions were observed in tumour samples.

The most common actionable mutations were on KRAS, PIK3CA, CDKN2A homozygous deletions, PTEN homozygous deletions, CCND1, FGFR1, MDM2, HER2 and HER1.

Molecular targeted therapies were recommended in 676 patients. Among them, 143 (7%) initiated a recommended molecular targeted therapy. Molecular targeted therapies received were mTOR inhibitors, anti-angiogenic tyrosine kinase inhibitors (TKI), EGFR TKI, inhibitors of cell cycle.

In patients with initiated molecular targeted agent therapy, median overall survival was 3.3 years and 5-year survival rate 34.8%. In patient in whom molecular targeted therapy was not initiated, the 5-year survival rate was 28.1%.

The authors concluded that in this series of cancer patients, CGH and NGS identified actionable alterations in more than half patients that led to treatment recommendation in 35%. Most patients treated derived benefit from the recommended molecular targeted therapy, but these represent a minority of the whole population screened.

ProfilER-2 is planned to compare the academic gene-panel with a commercial, 315 gene test from Foundation Medicine. This trial will assess whether screening a larger number of genes leads to more molecular targeted agent recommendations. The WES and WGS in routine screening are currently in preparation under France Medicine Genomics 2025 plan. The authors also questioned if there is a value of exploring patients in an earlier setting.

Reference

Tredan O, Corset V, Wang Q, et al. Routine molecular screening of advanced refractory cancer patients: An analysis of the first 2490 patients of the ProfilER Study. J Clin Oncol 35, 2017 (suppl; abstr LBA100)