ASCO 2017: Efficacy of cabazitaxel rechallenged in heavily-treated patients with metastatic castration-resistant prostate cancer (mCRPC)

Chicago, IL ( While docetaxel (DOC) has long been the primary chemotherapy option for the management of castration-resistant prostate cancer (CRPC), cabazitaxel (CABA) has established itself as a second-line therapeutic option.1 However, introduction of novel agents targeting the androgen receptor axis have provided competing options for physicians and patients.

There continues to be a population of patients who fail docetaxel and novel AR axis therapies as well. With such limited options, the ability to re-challenge patients with prior therapies may provide temporary benefit. The authors had previously demonstrated that docetaxel re-challenge for initial responders resulted in a progression-free interval of >6 months, but did not prolong survival.2

Along this vein, they aimed to assess the response to a cabazitaxel re-challenge in heavily pretreated patients with metastatic CRPC. Using a retrospective review, they identified 70 patients from 17 European centers, all of whom had received DOC, new hormal therapy (NHT, enza or abi) and CABA with a good response to CABA. Specifically, 52 received DOC-NHT-CABA, 15 DOC-CABA-NHT and 3 NHT-DOC-CABA. Primary outcomes were efficacy (PSA response, best clinical benefit), radiographic or clinical progression free survival (PFS), overall survival (OS), and safety. 

At the time of rechallenge, 83% had a high-volume disease (CHAARTED definition), 10% had visceral mets and 68 % were ECOG 0-1. Most had had a good response to first line androgen deprivation (> 12 months). Most were also symptomatic from the metastatic disease. 

CABA was rechallenged for a median of 6 cycles, but required prophylactic G-CSF in 47%. Median time from last CABA cycle was 8.6 months (mo). CABA rechallenge was tolerated well, with only 7 pts (10%) having grade 3-4 toxicity (neutropenia). 

Key outcomes are as follows: CABA rechallenge resulted in >30% PSA reduction in at least 41% of men, and resulted in clinical improvement (not defined) in 34%. Median progression-free survival (PFS) was 11.3 mo with DOC, 12 mo with NHT, 11.9 mo with first CABA (median 8 cycles), and 7.8 mo with CABA rechallenge. Median OS calculated from the first life-extending therapy was 59.9 mo (95% CI 47.8; 66.4); median OS benefit from the CABA rechallenge was 13.4 months.  

Limitations / Discussion Points:
1. As most patients were ECOG 0-1, clearly this is a healthy selected population that can tolerate multiple rounds of chemotherapy.
2. While the median time from last CABA cycle was 8.6 months, its unclear how long the interval was from the most recent therapy in the 15 who received NHT last.
3. Sequencing has been an important focus of recent discussion. It would have been nice to know if CABA rechallenge was more successful in the 15 patients who saw NHT last vs. CABA last. 

However, it would appear that CABA rechallenge does provide some PFS and OS benefit in heavily pretreated patients. It is limited to patients with good ECOG status who can tolerate additional therapy.

Presented By: Constance Thibault, MD, European George Pompidou Hospital, Paris, France; 

Co-Author(s): Jean-Christophe Eymard, Anne-Claire Hardy-Bessard, Alison J. Birtle, Michael Krainer, Giulia Baciarello, Aude Flechon, Sylvestre Le Moulec, Dominique Spaeth, Brigitte Laguerre, Orazio Caffo, Jean-Laurent Deville, Philippe Beuzeboc, Ali Hasbini, Marine Gross-Goupil, Carole Helissey, Mostefa Bennamoun, Stephane Oudard

Institution(s): Institut Jean-Godinot, Reims, France; Clinique Armoricaine de Radiologie, Saint-Brieuc, France; Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom; Department of Internal Medicine I, Vienna, Austria; Department of Cancer Medicine, Gustave Roussy Cancer Campus, Paris-Sud University, Villejuif, France; Centre Léon-Bérard, Lyon, France; Val-de-Grace Hospital, Paris, France; ORACLE, Centre d'Oncologie de Gentilly, Gentilly, France; Centre Eugène Marquis, Rennes, France; Medical Oncology, Santa Chiara Hospital, Trento, Italy; Hopital de la Timone, Marseille, France; Medical Oncology Department, Institut Curie, Paris, France; Clinique Pasteur, Brest, France; Centre Hospitalier-Universitaire Saint Andre, Bordeaux, France; HIA Bégin, Saint-Mandé, France; Department of Oncology, Institut Mutualiste Montsouris, Paris, France; Department of Medical Oncology, Hopital Europeen Georges Pompidou, AP-HP, Paris, France

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

1. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. doi: 10.1016/S0140-6736(10)61389-X.
2. Oudard S, Kramer G, Caffo O, Creppy L, Loriot Y, Hansen S, Holmberg M, Rolland F, Machiels JP, Krainer M. Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer. BJU Int. 2015 May;115(5):744-52. doi: 10.1111/bju.12845. Epub 2014 Dec 29.