ASCO GU 2018: Impact of Number of Cycles of Platinum-based First-line Chemotherapy for Advanced Urothelial Carcinoma

San Francisco, CA ( Neoadjuvant chemotherapy (NAC) prior to radical cystectomy for localized muscle-invasive bladder cancer (MIBC) and systemic chemotherapy for the treatment of locally advanced or metastatic bladder cancer are based on the use of platinum-based chemotherapy, specifically cisplatin. As the authors note, 6 cycles of platinum-based chemotherapy (CT) are conventionally utilized in this setting, but this chemotherapy is not without its associated toxicity, particularly cumulative toxicities. This can make it challenging to deliver the full 6 cycles of cisplatin-based chemotherapy. However, there is no prospective data on the number of cycles required for appropriate response.

In this large multi-institutional, international collaborative, the authors retrospectively address this issue. They utilized the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) database. They examined the association of the number of cycles of platinum-based first-line CT with overall survival (OS) after controlling for previously recognized prognostic factors used in a nomogram. The primary analysis was a comparison of < 6 cycles vs. ≥6 cycles – they excluded patients (pts) receiving < 3 or > 9 cycles to reduce confounding due to early removal for toxicities, progression and patient decision and increased number of cycles due to response and patient-related factors. Effectively they compared 3-5 cycles vs. 6-9 cycles of chemotherapy.

Of 1020 pts available from RISC, 472 (cisplatin = 338, carboplatin = 134) were evaluable for the landmark analysis with 281 events. Patients with OS < 6 months (n-496) were excluded. A total of 157 pts received 3-5 cycles (median 4) and 315 received 6-9 cycles (median 6). There was no significant difference between 3-5 vs. 6-9 cycles of platinum-based chemotherapy (HR 1.02, 95%CI: 0.77-1.33, p = 0.91). No significant interactions were observed with type of platinum (p = 0.09) and “completed planned CT” (p = 0.56). Interesting non-White patients did uniformly worse!

Sensitivity analyses: Comparison of 4 vs. 6 cycles (p = 0.57) and < 6 vs 6 vs 7-9 (p = 0.9) also yielded no significant differences for association with OS. No differential association was observed with survival for 3-5 vs. 6-9 cycles when examining by nomogram-defined risk group tertiles.

Obviously, while the authors already note this, the limitations of a hypothesis-generating retrospective analysis apply. Only a prospective analysis can remove any unknown confounders from the analysis. But, as this is a relatively rare condition, a large prospective study will be difficult. At this time, this may be the best data we have to say that maybe reducing the number of cycles of chemotherapy may not impair oncologic outcomes! The reduction in toxicity itself may make this worthwhile.

Speaker: Andrea Necchi, MD

Co-Authors: Luigi Mariani, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Aristotelis Bamias, Simon J. Crabb, Joaquim Bellmunt, Evan Y. Yu, Guenter Niegisch, Ulka N. Vaishampayan, Christine Theodore, Dominik R. Berthold, Sandy Srinivas, Srikala S. Sridhar, Elizabeth R. Plimack, Jonathan E. Rosenberg, Thomas Powles, Matthew Galsky, Guru Sonpavde

Institution(s): Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; University of Athens, Athens, Greece; Southampton Clinical Trials Unit, University of Southampton, Southampton, United Kingdom; Harvard Medical School/ Dana-Farber Cancer Institute, Boston, MA; Seattle Cancer Care Alliance, Seattle, WA; Heinrich-Heine University, Duesseldorf, Germany; Karmanos Cancer Center, Detroit, MI; Hospital Foch, Suresnes, France; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Stanford University, Stanford, CA; Princess Margaret Cancer Centre, Toronto, ON, Canada; Fox Chase Cancer Center, Philadelphia, PA; Memorial Sloan Kettering Cancer Center, New York, NY; Barts Health NHS Trust – St Bartholomew’s Hospital, London, United Kingdom; Icahn School of Medicine at Mount Sinai, New York, NY; Dana-Farber Cancer Institute, Boston, MD

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA