While treatment of localised AC is well established, there is paucity of data to inform the management of patient (pts) with advanced tumours. Thus we have retrospectively analysed treatment pathways and outcomes of a single institution series of advanced AC pts.
Inclusion criteria included epidermoid histology, inoperable locally recurrent or metastatic disease and availability of full medical records. The primary objective was overall survival (OS). Secondary objectives included objective response rate (ORR) and progression-free survival (PFS). Prognostic factors were analysed in a univariate model.
From 1997 to 2014, 64 pts were seen at The Royal Marsden NHS Foundation Trust who met the eligibility criteria. Pt characteristics were: females (60.9%), median age 59.2 (IQR: 52.1-66.4), history of HIV infection (7.8%), squamous histology (90.6%), metastatic disease (75%), median time to advanced disease 9.1 months (m) (IQR: 4.1-20.9), prior pelvic radiotherapy (82.8%), prior salvage surgery (15.6%). 51 pts (79.7%) received ≥1 line of systemic CT. Of these, 37% also underwent multimodality treatment including surgery, chemoradiotherapy or radiofrequency ablation. PF was the most common regimen prescribed in the first-line setting (74.5%) with an ORR of 34.4% (95% CI: 18.6-53.2). PTX-based CT (single agent or combination therapy with carboplatin) was used in 15 pts as either front line or salvage treatment and the overall ORR was 53.3% (95% CI: 26.6-78.7). Median PFS after first- and second-line CT was 5.8m (IQR: 2.8-7.6) and 3.2m (IQR: 2.5-7.1), respectively. Median OS in CT-treated pts was 15.4m (IQR: 10.0-45.2) and 13% were alive at 5 years. Age ≤65 years and liver metastases were predictive of better PFS (HR 0.39; 95% CI: 0.16-0.97, p = 0.04) and worse OS (HR 2.25; 95% CI: 1.25-4.03, p = 0.01), respectively.
This is the second largest series of advanced AC ever reported. Doublet CT with PF and PTX-based CT are active regimens in this setting. Prospective clinical trials are needed to standardise treatment pathways, investigate the potential of novel therapeutics and ultimately improve the modest survival outcome of this pt population.
Clinical trial identification
Legal entity responsible for the study
The Royal Marsden NHS Foundation Trust
The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research
I. Chau: Advisory roles with Merck Serono, Roche, Sanofi Oncology, Bristol Myers Squibb, Eli-Lilly, Novartis, Gilead Science. Research funding from Merck-Serono, Novartis, Roche and Sanofi Oncology. Honoraria from Roche, Sanofi-Oncology, Eli-Lilly, Taiho. D. Cunningham: Research funding from: Roche, Amgen, Celgene, Sanofi, Merck Serono, Novartis, AstraZeneca, Bayer, Merrimack and MedImmune. All other authors have declared no conflicts of interest.