Efficacy of afatinib in a patient with rare EGFR (G724S/R776H) mutations and amplification in lung adenocarcinoma: A case report

Abstract

BACKGROUND The most common EGFR mutations are in-frame deletions in exon 19 and point mutations in exon 21. Cases with classical EGFR mutations show a good response to EGFR tyrosine kinase inhibitors (TKIs), the standard first-line treatment. With the development of next generation sequencing, some uncommon genomic mutations have been detected. However, the effect of TKIs on such uncommon EGFR mutations remains unclear. CASE SUMMARY Here, we report a case of rare EGFR co-mutation in non-small cell lung cancer and the efficacy of afatinib on this EGFR co-mutation. A 64-year-old woman was diagnosed with thoracolumbar and bilateral local rib bone metastases, bilateral pulmonary nodules, and pericardial and left pleural effusion. The pathological diagnosis was lung adenocarcinoma. To seek potential therapeutic regimens, rare co-mutation comprising rare EGFR G724S/R776H mutations and amplification were identified. The patient experienced a significant clinical response with a progression-free survival of 17 mo. CONCLUSION A case of non-small cell lung cancer with rare EGFR G724S / R776H mutations and EGFR amplification responds well to TKI treatment.

Successful Treatment of Afatinib Reversing Epidermal Growth Factor ReceptorExon19Deletion/G724S MutationResistance Guided byProtein-DrugDocking

“…A previous case report of a patients with a G724S mutation showed a remarkable response to the combination of afatinib and osimertinib in 2017; however, tumor progressed rapidly in less than 3 months [1]. In the last half year, there have been several clinical cases that reported that afatinib was effective to G724S mutation [2–5], which is consistent with our results. In this manuscript, under the guidance of molecular docking results, we presented a patient with acquired Exon 19 Deletion(Ex19Del)/G724S mutation who was treated with afatinib and obtained long‐term clinical benefit of more than 20 months till now.…”

Afatinib treatment response in advanced lung adenocarcinomas harboring uncommon mutations

“…Patients with EGFR E709A/L858R, S720F/G719A, L747P, R776H/L858R, and L833V/H835L mutations also showed a TTF of more than 1 year, which was similar to the previous recommendations and increased our confidence to apply afatinib to these patients. 29,30,33 Presently, the mechanism of drug resistance of TKIs has also been widely concerned. For exon 19 deletions and exon 21 L858R mutations, the acquired EGFR T790M mutation is the primary resistance mechanism to first-and secondgeneration EGFR TKIs, followed by the acquisition of the second drive mutation; the emergence of new clones and the replacement of previously predominant clones; and the activation of some downstream pathways and histological transformations.…”

“…Patients with EGFR E709A/L858R, S720F/G719A, L747P, R776H/L858R, and L833V/H835L mutations also showed a TTF of more than 1 year, which was similar to the previous recommendations and increased our confidence to apply afatinib to these patients. 29 , 30 , 33 …”

An epidermal growth factor receptor compound mutation of L858R with S768I in advanced non-small-cell lung cancer: a case report

“…[ 36 ] 43 Female 19-Del + T790M Chemotherapy PD He et al . [ 37 ] 64 Female G724S + R776H Afatinib GR Bao et al . [ 38 ] 36 Male R670W + H835L + L833V Afatinib + osimertinib GR Yang et al .…”