Real-world treatment patterns in patients with advanced (stage III-IV) ovarian cancer in the USA and Europe.

Aim: To analyze real-world data relating to treatment decision-making in stage III-IV ovarian cancer (OC). Materials & methods: Real world data were collected from a survey of physicians and their patients (n = 2413) across Europe and the USA in 2017-2018. Results: 49% had stage IVb disease. 39, 54 and 7% of patients received first-line (1L), second-line, or 7% third-line or later treatment. In the 1L (ongoing or completed), 93% received platinum-containing regimens, 26% bevacizumab-containing regimens and 1% a PARP inhibitor-containing regimen. In 1L maintenance treatment, 81% received bevacizumab, 17% platinum-containing treatments and 6% a PARP inhibitor. Conclusion: The most common 1L treatment for advanced ovarian cancer was platinum-containing chemotherapy. Of those receiving 1L maintenance therapy, 70-99% (across countries) received targeted therapy.

Treatment Patterns and Health Outcomes in Platinum-Refractory or Platinum-Resistant Ovarian Cancer: A Retrospective Medical Record Review.

OBJECTIVE: The objective of this article is to describe real-world treatment patterns and outcomes in patients with platinum-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (PRROC) in the United States, United Kingdom, and Canada. METHODS/MATERIALS: Physicians retrospectively reviewed medical records of women aged 18 years or older who were diagnosed with PRROC between January 2010 and June 2014. Patient characteristics, initial PRROC therapy, and health care utilization were assessed; progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Data were obtained on 392 US, 296 UK, and 82 Canadian patients. At initial ovarian cancer diagnosis, 65.8% (United States), 93.3% (United Kingdom), and 82.9% (Canada) of patients had stage III/IV disease; 43.6%, 73.7%, and 56.1%, respectively, had high-grade tumors. At PRROC diagnosis, mean age was 57.2 years (United States), 59.2 years (United Kingdom), and 57.4 years (Canada). Eastern Cooperative Oncology Group performance status was 0/1 at PRROC diagnosis for 57.7% (United States), 80.1% (United Kingdom), and 36.6% (Canada) of patients. Most patients initiated systemic treatment after PRROC diagnosis (United States, 71.4%; United Kingdom, 83.1%; Canada, 81.7%). The most common initial PRROC therapy was pegylated liposomal doxorubicin monotherapy (United States, 18.6%; United Kingdom, 50.0%; Canada, 34.3%). During initial PRROC treatment, 80.7%, 59.8%, and 44.8% of patients had 1 office visit or more and 17.5%, 10.2%, and 14.9% of patients had 1 hospitalization or more in the United States, the United Kingdom, and Canada, respectively. Treatment toxicity was the most common reason for hospitalization (United States, 75.5%; United Kingdom, 64.0%; Canada, 80.0%). Median (95% confidence interval) PFS was 5.6 (4.9-6.2), 8.0 (6.8-9.2), and 6.4 (5.4-9.3) months in the United States, the United Kingdom, and Canada. The Cox proportional hazards model showed that stage III/IV, high-grade tumors, and poorer performance status were associated with shorter survival. CONCLUSIONS: Current treatments for PRROC yield limited PFS and frequent hospitalizations reported to be related to toxicities or procedural complications, suggesting a continued unmet need for more effective and tolerable therapeutic strategies for PRROC.

Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial.

BACKGROUND: Dacomitinib is an irreversible pan-EGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non-small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. We aimed to compare dacomitinib with erlotinib in a phase 3 study. METHODS: In a randomised, multicentre, double-blind phase 3 trial in 134 centres in 23 countries, we enrolled patients who had locally advanced or metastatic non-small-cell lung cancer, progression after one or two previous regimens of chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and presence of measurable disease. We randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. Randomisation was stratified by histology (adenocarcinoma vs non-adenocarcinoma), ethnic origin (Asian vs non-Asian and Indian sub-continent), performance status (0-1 vs 2), and smoking status (never-smoker vs ever-smoker). The coprimary endpoints were progression-free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wild-type tumours. The study has completed accrual and is registered with ClinicalTrials.gov, number NCT01360554. FINDINGS: Between June 22, 2011, and March 12, 2013, we enrolled 878 patients and randomly assigned 439 to dacomitinib (256 KRAS wild type) and 439 (263 KRAS wild type) to erlotinib. Median progression-free survival was 2·6 months (95% CI 1·9-2·8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] 0·941, 95% CI 0·802-1·104, one-sided log-rank p=0·229). For patients with wild-type KRAS, median progression-free survival was 2·6 months for dacomitinib (95% CI 1·9-2·9) and erlotinib (95% CI 1·9-3·0; stratified HR 1·022, 95% CI 0·834-1·253, one-sided p=0·587). In patients who received at least one dose of study drug, the most frequent grade 3-4 adverse events were diarrhoea (47 [11%] patients in the dacomitinib group vs ten [2%] patients in the erlotinib group), rash (29 [7%] vs 12 [3%]), and stomatitis (15 [3%] vs two [<1%]). Serious adverse events were reported in 52 (12%) patients receiving dacomitinib and 40 (9%) patients receiving erlotinib. INTERPRETATION: Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations. FUNDING: Pfizer.

Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042).

OBJECTIVES: Dacomitinib is a pan-HER inhibitor for advanced non-small-cell lung cancer (NSCLC). We explored the impact of a planned 4-day dacomitinib dose interruption on plasma exposure of dacomitinib and adverse events (AEs) of interest in Cohort III of the ARCHER 1042 study. MATERIALS AND METHODS: Patients, treatment-naïve for advanced NSCLC with EGFR activating mutations, received oral dacomitinib 45mg QD (once daily). A planned dose interruption occurred in Cycle 1 from Days 11 through 14. The primary endpoint was the pharmacokinetic (PK) characteristics of dacomitinib in Cycle 1Day 10 and during dose interruption. Secondary endpoints included safety and concomitant medications used to treat AEs of interest. RESULTS: Cohort III enrolled 25 patients. Median plasma Cmax of dacomitinib in Cycle 1 Day 10 was 83.40ng/mL. Average median plasma dacomitinib concentration during the 4-day dose interruption was 42.63ng/mL. In the first 8 weeks of treatment 1) 80% of patients used concomitant medications for dermatologic AEs, 76% for diarrhea, and 44% for stomatitis, and 2) all patients experienced treatment-emergent AEs and 28% had all-causality Grade 3 AEs. CONCLUSION: At 45mg QD dosing, PK parameters of plasma dacomitinib in Cycle 1 Day 10 were comparable to that obtained in Cycle 1 Day 14 from other dacomitinib studies. Average median plasma dacomitinib concentration during the 4-day dose interruption was approximately half of the median plasma Cmax of dacomitinib observed prior to dose interruption. The toxicity profile was consistent with that from other studies of dacomitinib.