Genomic profiling of ctDNA in advanced NSCLC feasible in HK

Christina Lau
22 Nov 2017
Genomic profiling of ctDNA in advanced NSCLC feasible in HK
Dr Herbert Loong

Genomic profiling of circulating tumour DNA (ctDNA) is feasible in the management of advanced non-small-cell lung cancer (NSCLC) and prompts changes in matched therapy in selected patients, a retrospective study in Hong Kong has shown.

“The US National Comprehensive Cancer Network [NCCN] guidelines have recommended seven genomic biomarkers for NSCLC, namely EGFR, ALK, BRAF, ERBB2 [HER2], MET, RET and ROS1. In our study, genomic profiling of ctDNA detected alterations in the majority of patients with advanced NSCLC, with targetable aberrations and resistance mechanisms identified,” reported first author Dr Herbert Loong of the Department of Clinical Oncology, Chinese University of Hong Kong (CUHK), at the ESMO Asia 2017 Congress. [ESMO Asia 2017, abstract 1373]

The researchers retrospectively reviewed data of 76 patients with advanced or metastatic NSCLC (median age, 59.6 years) whose physician requested ctDNA-based genomic profiling using the Guardant360 platform between January 2016 and June 2017. In the cohort, seven patients had squamous cell carcinoma, 10 had adenocarcinoma, and 58 had NSCLC not otherwise specified (NSCLC-NOS).

EGFR mutation and EML4-ALK fusions were found to be the most common genomic alterations in our Asian cohort. Other alterations, including ERBB2, MET, ROS1 and BRAF V600E, accounted for 30 percent of all detectable alterations,” said Loong.

Among the 68 patients with adenocarcinoma or NSCLC-NOS, 62 (91 percent) had ctDNA variants identified (median, 3 variants per sample). Of these patients, 26 (41.9 percent) had an alteration in one of the seven NCCN-recommended genomic biomarkers. The most common alteration was activating EGFR mutation (n=13; 21 percent [activating EGFR + T290M, n=3]), followed by EML4-ALK fusion (n=5; 8.1 percent) and ERBB2 exon 20 insertion (n=4; 6.5 percent). In addition, two patients (3.2 percent) had MET amplification, while ROS1 fusion and BRAF V600E mutation occurred in one patient each (1.6 percent).

In the seven patients with squamous cell carcinoma, all had multiple detectable variants identified (median, 6 variants per sample). Three patients had FGFR1 amplification, two had ERBB2 amplification, and one had PIK3CA amplification.

“Genomic profiling of ctDNA led to changes in matched therapy in some patients,” said Loong.

Loong reported the case of a 48-year-old male patient with metastatic ALK-positive NSCLC, who achieved good partial response (PR) to first-line crizotinib therapy for 15 months. On disease progression, the patient was recruited into a clinical trial of second-line therapy with ceritinib plus nivolumab, and achieved good PR for 18 months. The patient’s disease then progressed again, with genomic profiling of ctDNA showing EML4-ALK fusion and MET exon 14 skipping variant. He was rechallenged with crizotinib and had good PR for more than 6 months.

“Genomic profiling is an effective alternative to repeat invasive biopsy in patients with advanced cancer. It is more comprehensive than tissue-based assays, with the ability to provide a summary of tumour heterogeneity. Our findings demonstrate the feasibility of implementing genomic profiling of ctDNA in patients with advanced NSCLC in Asia,” he concluded.

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