Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with increased penetration across the blood brain barrier compared to previous EGFR TKIs and thus a 52% reduction in the risk of intracranial disease progression is seen when it is used as 1st line of therapy compared to gefitinib and erlotinib. It is also efficient as 2 nd line therapy for patients who developed the T790M resistance mutation following treatment with previous generation TKIs. Here, we report eleven patients who were treated by an increasing dose of osimertinib from 80 mg to 160 mg QD orally following intracranial progression in either 1 st or 2 nd line setting. Methods This is a sub-cohort analysis from a larger non-randomized, phase 2, open-label trial, evaluating the efficacy of osimertinib dose escalation from 80 to 160mg in EGFR mutated advanced NSCLC patients with intracranial progression in either 1 st (Arm A) or 2 nd line setting (Arm B for T790M+ and C for T790M-). Results Eleven patients, five in arm A, four in arm B and two in arm C were reported in this study. The mPFS of osimertinib before dose escalation was 11.4±8.9(6.6-30.7) months for arm A, 8.7±1.8(6.3-11.2) for arm B, and 14.5±7.8(6.7-22.3) for arm C. Intracranial response rate to dose-escalation was 54%(6/11) with 2/11 having intracranial stability. Median iPFS was 4.3±7.4(0.7-25.5) months; 3.8±6.4(1.8-18.9), 5.6±9.7(0.7-25.5) and 7.0±2.7(4.3-9.6) for arms A/B/C respectively. Dose escalation was well tolerated with diarrhea and paronychia as the main dose limiting symptoms. Conclusions Osimertinib 160 mg is feasible and may offer a therapeutic alternative for patients with isolated intracranial progression on osimertinib standard (80mg) dose. Further studies on CNS osimertinib pharmacokinetics are needed to test this hypothesis.

of grade 3 or higher), and did not cause a delay in surgery. Patients' nutritional status and QOL improved significantly. R0 resection rate is 100%, with MPR 21/29 (72.4%), pCR 12/29 (41.4%), and ORR 28/29 (96.6%). No perioperative death has occurred so far. Conclusion:Pembrolizumab combined with paclitaxel and cisplatin as a neoadjuvant therapy was associated with few side effects, did not delay surgery, and induced a major pathological response in 72.4% of resected ESCC tumors. It may be better than the neoadjuvant concurrent chemoradiation recommended by NCCN guidelines.

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The authors report on a case of treatment-related myocardial infarction in a young man receiving chemotherapy (BEP) for testicular cancer and discuss the implications of the case.

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