Osimertinib for compound EGFR exon 19 deletion/T790M mutated lung squamous cell carcinoma

Abstract

The role of the epidermal growth factor receptor (EGFR) mutation status testing in lung squamous cell carcinoma (SqCC) remains controversial. Evidence of the effectiveness of osimertinib in SqCC with EGFR T790M mutation is limited. Here, we describe a hitherto unreported case of a stage III SqCC patient with compound mutation of EGFR exon 19 deletion (19Del) and T790M mutation. Pathological complete tumor response was achieved after treatment with osimertinib. We suggest that EGFR mutation testing should be performed in Asian patients who have not been definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a “primary” resistance mechanism (EGFR T790M). Key points An unreported case of stage III squamous cell carcinoma with synchronous occurrence of EGFR exon 19 deletion (19Del) and T790M mutation. Complete tumor response was achieved after treatment with osimertinib. EGFR mutation testing should be performed in Asian patients who are not definitively diagnosed with SqCC due to small lung biopsy samples. Osimertinib has shown good efficacy in SqCC harboring a “primary” resistance mechanism (EGFR T790M).

Next‐generation sequencing clarified why first‐line treatment with osimertinib was ineffective in an autopsied case of EGFR‐mutated lung squamous cell carcinoma

“…However, osimertinib was used as first-line therapy only in three cases. 10,11 The poor clinical outcome of patients with SCC despite receiving molecular-targeted therapy has also been demonstrated in a previous study. 12 Multiple EGFR mutations may affect the efficacy of tyrosine-kinase inhibitors in SCC.…”

“… 4 This improvement in PFS and OS in lung SCC is worse than that reported in patients with lung adenocarcinoma. 4 Several reports have shown the efficacy of third‐generation EGFR tyrosine‐kinase inhibitors, including osimertinib, in lung SCC, 5 , 6 , 7 , 8 , 9 , 10 , 11 as described in Table 3 . However, osimertinib was used as first‐line therapy only in three cases.…”

“…Several reports have shown the efficacy of third‐generation EGFR tyrosine‐kinase inhibitors, including osimertinib, in lung SCC, 5–11 as described in Table 3. However, osimertinib was used as first‐line therapy only in three cases 10,11 …”

Efficacy of osimertinib for lung squamous cell carcinoma with de novo EGFR T790M‐positive: Case report and literature review

“…To the best of our knowledge, a literature search for case reports of osimertinib in SCC patients with EGFR mutation‐positive tumors, yielded 16 cases, including the present case 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 (Table 1 ). The treatment outcome breakdown was 12 cases of PR and four cases of PD, and many were reported to be effective, but the duration of response was limited in some cases.…”

An Unexpected Diagnosis of Second Primary Malignancy in a Breast Cancer Survivor: A Case Report

“…As seen in our patient, the most common EGFR sub-mutations are exon 19 deletions, with a prevalence ranging from 40% to 67% [ 18 ]. This particular sub-mutation leads to hyper-activation of pro-survival and anti-apoptosis signaling pathways, thus conferring favorable outcomes in patients treated with EGFR-TKI drugs, like the first-generation TKI erlotinib [ 19 ]. Initially, our patient was initiated on erlotinib, but after eight months, resistance set in due to the acquisition of the T790M mutation in the EGFR gene, which occurs in approximately 50% of patients who become resistant to first- or second-generation EGFR TKIs [ 20 ].…”