First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.

INTRODUCTION: The safety and efficacy of first-line durvalumab in PS2 patients with advanced NSCLC is unknown. Here, we present the primary analysis of first-line durvalumab in PS2 patients, unsuitable for combination chemotherapy. METHODS: In this single-arm, multicenter, phase II trial patients with PD-L1 positive (tumor proportional score ≥25%), advanced NSCLC with PS2, received four-weekly durvalumab 1500 mg. The primary endpoint was overall survival (OS) at 6 months. RESULTS: Forty-eight patients were included. Median follow-up was 23.3 months (95% CI: 14.3-28.6). OS at 6 months was 60% (95% CI: 45-74%). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median progression free survival were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1), respectively. Thirty-three deaths were observed at the time point of the analysis. Seven early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failure in patients with advanced symptomatic primary lung tumors. Three more early fatal events occurred after exclusion of patients with grade ≥ 3 dyspnea. Treatment-related AEs ≥G3 were reported in 9 patients (19%) and included colonic perforation in one patient (grade 5), colitis in 4 patients (8%), increased lipase in 3 patients (6%), and hepatitis in 2 patients (4%). CONCLUSIONS: First-line durvalumab in PS2 patients with advanced PD-L1 positive NSCLC results in a high number of early fatal events. When patients with grade ≥ 3 dyspnea are excluded a promising 6-month OS with an acceptable toxicity profile can be observed. Durvalumab could be an option instead of single agent chemotherapy for PS2 patients who are not candidates for platinum doublet chemotherapy provided they are well selected.

Do YOU know the Ki-67 index of your breast cancer patients? Knowledge of your institution's Ki-67 index distribution and its robustness is essential for decision-making in early breast cancer.

OBJECTIVES: The proliferative activity of the Ki-67 index is important in decision-making of adjuvant treatments in early breast cancer. Its reliability can be reduced by inter-observer variability. This analysis' objective is to evaluate the robustness of Ki-67 values within one center over 5 years and to compare its distribution with a published dataset. MATERIALS AND METHODS: Ki-67 indices of early breast cancers treated at St. Gallen Breast Center were collected (2010-2014; 1154 patients). Distribution of Ki-67 values was analyzed for each year, along with histologic subtype and grading. Tumors were classified into intrinsic subtypes using two definitions: 2013 St. Gallen Consensus and the refined definition by Maisonneuve ("Milano Group"). Our institution's Ki-67 cut-off value was adjusted to obtain the same distribution of luminal subtypes as published data of the Milano Group. RESULTS: Ki-67 index frequency distributions were comparable between years (mean 26-30%, median 22-26%). Shape and position of the distribution curves were nearly identical. Ki-67 values correlated with tumor grade (median Ki-67: G1: 12.0%, G2: 21%, G3: 38%). Standard deviation of Ki-67 increased with higher grading (G1: 6.9; G2: 9.2; G3: 18.2; p < 0.001). According to the 2013 definition (and refined definition respectively), there were 35% (41%) luminal A-like and 65% (59%) luminal B-like tumors. To obtain the same distribution as the Milano group, Ki-67 cut-off needed to be elevated to 22%. CONCLUSIONS: Ki-67 index assessment was comparable over many years. Knowledge of one's institution's Ki-67 value distribution is essential for clinical decision-making of adjuvant therapies in early breast cancer.

Carboplatin dose based on actual renal function: no excess of acute haematotoxicity in adjuvant treatment in seminoma stage I.

INTRODUCTION: The practice of carboplatin dosing is not concordant among different centres and oncologists. Some clinical guidelines recommend capping of the carboplatin dose at, for example, creatinine-clearance (Crea-Cl) of 125 mL/min because of concerns of excessive toxicity. Clinical data to support such recommendations are lacking, especially in patients with seminoma. METHODS: This is a retrospective analysis of acute haematotoxicity of patients with stage I seminoma treated with adjuvant carboplatin area under the curve (AUC) 7 in routine practice in two Swiss centres in 2005-2015, and a comparison of incidence and grade (according to Common Terminology Criteria for Adverse Events v4.0) of haematological adverse events (hAEs) in patients with Crea-Cl <125 mL/min vs >125 mL/min without dose capping. RESULTS: 74 patients with 229 documented measurements were included (median 3/patient). A total of 151 hAEs occurred. Platelet nadir occurred earlier than median white cell/neutrophil count (median day 15 vs day 22; P<0.0001). The majority of hAEs were mild, with more than 80% being of grade 1. Only two (2.7%) clinically relevant hAEs necessitating subsequent interventions occurred (one patient received platelet transfusion, one patient with febrile neutropaenia). Haematological toxicities were not statistically different in patients dosed with Crea-Cl >125 mL/min versus those with Crea-Cl <125 mL/min. No hAEs other than grade 1 occurred before day 10 and after day 24. CONCLUSIONS: Toxicity after single-dose carboplatin AUC 7 is generally mild. No excess of toxicity occurs in patients with high Crea-Cl above 125 mL/min, and therefore dose capping is not routinely necessary. In addition, this study provides a rationale for efficient use of healthcare services without compromising patients' safety.