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PURPOSE Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non–small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone. METHODS We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life. RESULTS The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [ P < .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [ P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group. CONCLUSION Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.

Treatment with gefitinib alone for chemotherapy-naïve NSCLC patients with EGFR mutations could achieve a high efficacy with acceptable toxicity. To assess the proper timing of gefitinib in such patients, a subsequent randomized trial comparing gefitinib with standard chemotherapy is warranted.

Highlights d PKM1 promotes tumor growth cell intrinsically in some contexts d PKM1 activates glucose catabolism without interfering with biosynthetic pathways d PKM1-dependent autophagy/mitophagy contributes to malignancy d Expression of PKM1, but not PKM2, is sufficient to support SCLC cell proliferation

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Epithelial stratification in the RCC is caused by inflammation that may extend into the adjacent adenohypophysis or neurohypophysis and overwhelm the hypophysis, resulting in panhypopituitarism. Transsphenoidal excision may represent the best choice for treatment, at least for cases of RCC in which there is partial impairment of hypophysial function.

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Monitoring of cfDNA by dPCR is informative for prediction of afatinib efficacy, whereas that by NGS is reliable and has the potential to identify mechanisms of treatment resistance.