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.

IntroductionThe 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.MethodsThis 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.Results74 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.ConclusionsToxicity 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.

No abstract

No abstract

9088 Background: The safety and efficacy of 1L durvalumab in PS2 patients (pts) with advanced NSCLC is unknown. Important safety data leading to exclusion of pts with relevant respiratory symptoms have been published as an interim report. Here we present the primary analysis of 1L durvalumab in PS2 pts, unsuitable for combination chemotherapy and PD-L1 expression in ≥25% of tumor cells. Methods: In this single-arm, multicenter, phase II trial pts with PD-L1 positive (tumor proportional score, TPS ≥25%), advanced NSCLC with PS2, unsuitable for combination chemotherapy determined by the investigators, in the absence of known contraindications for immunotherapy and sufficient organ function, received a fixed dose of 1500 mg durvalumab every four weeks. The primary endpoint was overall survival (OS) at 6 months. The statistical hypothesis was to improve OS at 6 months from ≤35% to ≥53%. Adverse events (AEs) were assessed according to National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 5.0. Results: Forty-eight pts were included (29 males, 19 females). Median age was 76 years (range, 37-87). OS at 6 months was 60% (95% CI: 45-74%). OS at 6 months after the exclusion of pts with initially relevant respiratory symptoms was 67% (95% CI: 46-84%, n = 27) compared to the subgroup of pts without this exclusion criteria who were recruited before the amendment (52%, 95% CI: 30-74%, n = 21). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median PFS were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1). Thirty-three deaths (69%) were observed to date. Ten 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 failures in pts with advanced symptomatic primary lung tumors. Only 3 more early fatal events occurred after the protocol amendment excluding pts with severe respiratory symptoms. Thirty-nine patients (81%) had an AE grade ≥3 (G3). The most frequent AEs ≥G3 were lung infection (19%), dyspnea (15%) and hypertension (10%), respectively. Treatment-related AEs ≥G3 were reported in 9 pts (19%) and included colonic perforation in one patient (grade 5), colitis in 5 pts (10%), hepatitis and increased lipase in 3 pts each (6%). Conclusions: 1L durvalumab in PS2 pts with advanced PD-L1 positive (TPS ≥25%) NSCLC is effective and led to a promising 6-month OS of 60%. Four-weekly durvalumab can be safely offered to pts presenting without severe pulmonary symptoms who are not candidates for chemotherapy. Clinical trial information: NCT03620669 .