TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

Background The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum–pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. Patients and methods Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m 2 or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m 2 every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m 2 Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib–chemotherapy combination. Results Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib–carboplatin–pemetrexed, 100%; osimertinib–cisplatin–pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib–carboplatin–pemetrexed and nausea (60%) with osimertinib–cisplatin–pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. Conclusions Osimertinib–chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase.

on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival analyzed on an intention-totreat basis. Adverse events were assessed according to treatment received. Results: Between 22 May 2015 and 12 March 2018, 503 patients were randomly allocated to treatment. Median overall survival was 13.6 months (95% CI, 10.9e16.5) for the 251 patients allocated to docetaxel and 16.2 months (95% CI, 14.4e19.0) for the 252 patients allocated to nab-paclitaxel (hazard ratio, 0.85; 95.2% CI, 0.68e1.07). Median progression-free survival was 4.2 months (95% CI, 3.9e5.0) for the nab-paclitaxel group versus 3.4 months (95% CI, 2.9e4.1) for the docetaxel group (hazard ratio, 0.76; 95% CI, 0.63e0.92; p¼0.0042). The objective response rate was 29.9% (95% CI, 24.0e36.2) for the nab-paclitaxel group and 15.4% (95% CI, 10.9e20.7) for the docetaxel group (p¼0.0002), and it showed a significant improvement for nabpaclitaxel versus docetaxel regardless of tumor histology. Adverse events of grade 3 included febrile neutropenia (55 [22%] of 249 patients in the docetaxel group versus 5 [2%] of 245 patients in the nab-paclitaxel group) and peripheral sensory neuropathy (2 [1%] versus 24 [10%], respectively). Conclusion: The trial showed that nabpaclitaxel was noninferior to docetaxel in terms of overall survival. Nab-paclitaxel should thus be considered a standard treatment option for previously treated patients with advanced NSCLC.

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Background: Osimertinib, a 3rd-generation, CNS-active, oral EGFR-TKI, showed superior efficacy vs comparator EGFR-TKIs (erlotinib/gefitinib) in treatment-naïve EGFRm advanced NSCLC (median OS 38.6 vs 31.8 months; median PFS 18.9 vs 10.2 months). Gefitinib plus carboplatin/pemetrexed chemotherapy has shown improved ORR and PFS vs gefitinib alone. Combining osimertinib with platinum/pemetrexed may further improve patient outcomes.