Role Of Tumor DNA Profiling For EGFR Mutation Status At Baseline In Lung Cancer When Liquid Biopsy Fails!!

Dr. Palanki Satya Dattatreya,

Director and Chief of Medical Oncology Services, Renova Hospitals, Hyderabad

This is a case which is unique in terms of how liquid biopsy could fail sometimes and tissue remains the gold standard for EGFR mutation status assessment.

Clinical Presentation and Diagnosis

A 65-year-old female who initially complained of vomiting and giddiness was diagnosed with adenocarcinoma of left lung with brain metastases. Going for a tissue biopsy was a challenge, considering the COVID condition, for her safety as cancer patients usually present a compromised immune system, she went through liquid biopsy testing and the EGFR status was negative. Patient was started on chemotherapy with Cisplatin+Pemetrexed which is the standard of care for NSCLC patients adopted from NCCN guidelines. There was a partial response post three-months follow-up. Being a very classical presentation (Asian woman, non-smoker, adenocarcinoma), the clinician wanted to further rule out the possibility of any EGFR mutation in this patient by doing a tissue biopsy. Comprehensive NGS profiling was advised along with EGFR mutation.

Summary of CGP of Patients Tumor Sample

We identified Leu858Arg variant in the EGFR gene (exon 21) with mutant allele burden of 5% (Read support of 5 mutant reads and hence low allelic burden). The results were further confirmed by reflex testing using qPCR test and it was concordant. This anecdotal evidence helped the clinician in planning the targeted treatment for the benefit of the patient.

The corroborated findings from baseline liquid biopsy and tissue for EGFR mutation status also provides a prognostic value addition to understand the biology of disease in this patient. It has been well proven in clinical trials LUX lung III and LUX lung VI, that those patients whose tumor does not bleed EGFR mutant clones into circulation i.e tissue positive for EGFR and liquid biopsy negative for EGFR, have been shown to have a significantly improved progression free survival (PFS) and overall survival (OS) as compared to the other category of patients whose EGFR mutation status is positive both on tumor and liquid biopsy.