The survival outcomes of the FLAURA trial support osimertinib as the new standard of care for untreated patients harboring activating mutations in the epidermal growth factor receptor (EGFR). Despite the initial response, disease progression invariably occurs. Although uncommon, BRAF V600E mutation arises as a unique mechanism of resistance, and thus far, no prospective studies are available to support concurrent EGFR/BRAF blockade. We report a case of impressive radiological and ctDNA response under dabrafenib, trametinib, and osimertinib in an advanced EGFR-mutant lung adenocarcinoma patient who developed BRAF V600E as one of the acquired resistance mechanisms to second-line osimertinib. Moreover, the patient experienced remarkable clinical improvement and good tolerance to combination therapy. The present case suggests the importance of prospective studies evaluating both efficacy and safety of the combination in later line settings and points towards the potential of ctDNA to monitor resistance mechanisms and treatment benefit in clinical practice.
Osteonecrosis is a multifactorial process that can affect different skeletal structures of the body. Osteonecrosis of the jaw associated with bevacizumab, steroids and bisphosphonates, alone or in combination, is a well-documented phenomenon. There are few cases of involvement of the appendicular skeleton. Magnetic resonance imaging is the most sensitive method for diagnosis. We hereby report two cases of osteonecrosis in the right tibia and in bilateral femoral heads in patients with adenocarcinoma of the lung and ovarian papillary serous carcinoma, respectively, that developed the complication after long-term bevacizumab exposure. Long-term exposure to antiangiogenic treatment may be a potential risk factor. Oncologists should be aware that osteonecrosis is a rare but real toxicity associated with bevacizumab and other antiangiogenics, which can occur in locations different from the jaw.
Osimertinib is a first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. Pneumonitis is a severe adverse event (AE) related to osimertinib treatment which appears to be more frequent when associated with concurrent or previous anti-PD(L)1 exposure. Data regarding the efficacy and safety of osimertinib rechallenge, especially in the setting of central nervous system (CNS) metastases, are scarce. We herein describe a case of a 53-year-old patient with metastatic EGFR-mutated NSCLC, who developed pneumonitis after osimertinib treatment and was successfully rechallenged with 40 mg daily osimertinib, with CNS response. This dose reduction strategy may be an option for selected patients with brain metastases after tyrosine kinase inhibitors-induced AEs.
Background
The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes’ homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.
Case presentation
We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.
Conclusions
Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.
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