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Acquired drug resistance: 11 case reports In a retrospective study of 62 patients with metastatic EGFR-mutant lung cancer, 11 patients [ages and sexes not stated] were described, who acquired resistance to osimertinib or alectinib during treatment for metastatic EGFR-mutant lung cancer. All the patients, who had metastatic EGFR-mutant lung cancer, started receiving osimertinib. Two of these patients, who received later-line osimertinib, additionally received alectinib. However, 9 patients acquired resistance to osimertinib via histologic transformation, with squamous cell transformation (n=5; patients 1–5 from figure 4), pleomorphic transformation with squamous, sarcomatoid and small cell features (n=1; patient 6 from figure 4) and small cell transformation (n=3; patients 7–9 from figure 4). Two patients acquired resistance to osimertinib and alectinib, wherein 1 patient acquired an EGFR C797S mutation and lost an ALK fusion following treatment with osimertinib and alectinib, and 1 patient acquired an ALK G1202R mutation following treatment with osimertinib and alectinib [durations of treatments to reactions onsets not stated]. Therefore, the 9 patients, who acquired resistance to osimertinib via histologic transformation, were treated with subsequent lines of chemotherapy, which included carboplatin, pemetrexed, docetaxel, gemcitabine, vinorelbine, pembrolizumab, etoposide, paclitaxel, radiotherapy followed by osimertinib, resection followed by chemoradiotherapy, bevacizumab, ipilimumab or nivolumab. Five of these patients died after 3–19 months, 1 patients exhibited progression, and 3 patients had been receiving treatment [outcomes not stated]. Schoenfeld AJ, et al. Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in EGFR803497868 Mutant Lung Cancer. Clinical Cancer Research 26: 2654-2663, No. 11, Jun 2020. Available from: URL: http://doi.org/10.1158/1078-0432.CCR-19-3563

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Reactions 22 Aug 2020 No. 1818