<p>Durable Clinical Response of Advanced Lung Adenocarcinoma Harboring <em>EGFR-19del/T790M/BRAF^V600E</em> Mutations After Treating with Osimertinib and Dabrafenib Plus Trametinib: A Case Report</p>

Abstract

EGFR-T790M and BRAF V600E are the common resistance mechanisms to EGFRtyrosine kinase inhibitors (TKIs). Standard treatment for the triple mutations of EGFR-19del, T790M, and BRAF V600E is still under debate. Herein, we present a case of therapeutic efficacy of osimertinib and dabrafenib plus trametinib on a 63-year-old man with advanced lung adenocarcinoma. This patient reached a remarkable progression-free survival of 9 months without any serious adverse reaction. At the progression of the disease, C797S mutation in cis was detected by liquid biopsy. Subsequently, brigatinib with cetuximab was administered but no curative effect was observed. Then, therapy was changed to apatinib combined with osimertinib. The subsequent CT scan showed that the lesions reached stable disease (SD), and the survival benefit has been evaluated. This case showed that the combination treatment of osimertinib and dabrafenib plus trametinib might be a great treatment option for NSCLC patients with triple mutations (EGFR-19del/T790M/BRAFV600E).

Transformation of non-small cell lung cancer into small cell lung cancer in a patient with advanced lung cancer: a case report

“…Several studies have revealed that the most frequent mechanisms underlying resistance to EGFR TKIs were the occurrence of EGFR gene mutations and SCLC transformation. 1,3,8 The patient in our case had EGFR ex19del before his initial treatment. However, EGFR exon20p.T790M point mutation, EGFR amplification, MYC amplification, RB1 exon 2 truncated mutations, and TP53 exon 5 frameshift mutations were detected after gefitinib treatment.…”

“… 2 Targeted therapy inhibits the activity of epidermal growth factor receptor (EGFR) or other specific proteins known to be mutated. 3 However, most patients with NSCLC rapidly acquire drug resistance to EGFR tyrosine kinase inhibitors (TKIs). 4 The mechanisms of acquired drug resistance are complex and include the development of new gene mutations, transformation of NSCLC into SCLC, 5 and combination of NSCLC and SCLC histological subtypes at diagnosis.…”

Possibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐cis‐C797S mutations in lung adenocarcinoma patients

“…However, not all the patients who received brigatinib achieved a desirable efficacy. Another case report showed a patient who was treated by brigatinib and cetuximab progressed in only 1 month 18 . A retrospective study compared the clinical efficacy of brigatinib combination with cetuximab and chemotherapy.…”

Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling

“… 47 Another patient with advanced lung adenocarcinoma carrying EGFR -19del, T790M and B-RAF V600E mutations that received a similar three-drug combination treatment achieved a striking progression-free survival of 9 months and did not show any serious adverse reaction. 48 The same treatment regimen was also used to treat two NSCLC patients carrying EGFR 19del, T790M, and B-RAF V600E mutations in another case report, in which clinical response in one patient lasted for 13.4 months, but not in the other patient. 49 Similarly, the treatment of two cases of advanced NSCLC patients carrying EGFR 19del or L858R, T790M and B-RAF V600E mutations with osimertinib and the B-Raf V600E inhibitor, vemurafenib, combination achieved a noticeable improvement in clinical symptoms including physical mobility within 4 to 6 weeks from the initiation of the combination treatment.…”