Switch to EGFR-TKI after upfront platinum doublet induction therapy in non-small cell lung cancer (NSCLC) patients with EGFR (Epidermal Growth Factor Receptor) mutation: A multicentre retrospective study.

Introduction of EGFR-TKI has changed the treatment paradigm for NSCLC patient with activating mutations of EGFR exons 18-21, replacing chemotherapy as standard first line treatment. Given the delays in molecular study results we sometimes face the need to start treatment in very symptomatic patients with high tumor burden. The reason for this retrospective study is to analyze the survival impact of performing an induction cytotoxic therapy until obtaining the molecular profile (EGFR mutation), followed by targeted therapy. This is a retrospective analysis of 31 patients who did upfront chemotherapy (ChT) before switching to EGFR TKI upon the molecular profile result. The calculated survival endpoints were progression-free survival (PFS), duration of TKI response and overall survival (OS). All patients were treated with upfront chemotherapy with a median of one cycle (range 1-3) followed by a first generation EGFR-TKI. Median PFS was 13 months (95% CI, 6.6-19.4) and median OS 33 months (95% CI, 11.9-54.0). After first line progression 14 patients were treated with Osimertinib. In this subgroup median OS was 52 months (95% CI, 34.0-69.9). In the multivariable Cox model, only body mass index retained independent prognostic significance for progression-free survival (p = 0.045). Survival outcomes in this cohort are in line with published data regarding first generation EGFR-TKI, both in terms of PFS and OS. Despite the limitations of this study, starting with upfront chemotherapy doesn't seem detrimental in terms of survival outcomes, with the potential advantage of symptomatic control. To our knowledge, this is the first study to address this strategy, which requires further confirmation.

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma.

BACKGROUND: Malnutrition and sarcopenia are poor prognostic factors in many cancers. Studies in gastric and esophageal (GE) cancer have focused on curative intent patients. This study aims to evaluate the prognostic utility of malnutrition and sarcopenia in de novo metastatic GE adenocarcinoma. METHODS: Patients with de novo metastatic GE adenocarcinoma seen at the Princess Margaret Cancer Centre from 2010 to 2016 with an available pre-treatment abdominal computed tomography (CT) were included. Malnutrition was defined as nutritional risk index (NRI) <97.5. Skeletal muscle index (SMI) was measured at the L3 level (sarcopenia defined as SMI <34.4 cm2 /m2 in women and <45.4 cm2 /m2 in men). Patients receiving chemotherapy had NRI and SMI recalculated at the time of first restaging CT. RESULTS: Of 175 consecutive patients, 33% were malnourished and 39% were sarcopenic at baseline. Patients with pretreatment malnourishment had significantly shorter overall survival (OS; 5.8 vs. 10.9 months, p = 0.000475). Patients who became malnourished during chemotherapy had worse OS compared to those who maintained their nutrition (12.2 vs. 17.5 months p = 0.0484). On univariable analysis, ECOG (p < 0.001), number of metastatic sites (p = 0.029) and NRI (p < 0.001) were significant prognostic factors while BMI (p = 0.57) and sarcopenia (p = 0.19) were not. On multivariable analysis, ECOG (p < 0.001), baseline NRI (p = 0.025), and change in NRI during treatment (p < 0.001) were significant poor prognostic factors for OS. CONCLUSIONS: In de novo metastatic GE adenocarcinoma patients, ECOG, pretreatment NRI and change in NRI were significant prognostic factors for OS while sarcopenia was not. Use of NRI at baseline and during treatment can provide useful prognostic information.