Nicolas Delanoy1, Anne-Claire Hardy-Bessard2, Eleni Efstathiou3, Sylvestre Le Moulec4, Umberto Basso5, Alison Birtle6, Alastair Thomson7, Michael Krainer8, Aline Guillot9, Ugo De Giorgi10, Ali Hasbini11, Gedske Daugaard12, Amit Bahl13, Simon Chowdhury14, Orazio Caffo15, Philippe Beuzeboc16, Dominique Spaeth17, Jean-Christophe Eymard18, Aude Fléchon19, Jérôme Alexandre20, Carole Helissey21, Mohamed Butt22, Frank Priou23, Éric Lechevallier24, Jean-Laurent Deville24, Marine Gross Goupil25, Rafael Morales26, Antoine Thiery-Vuillemin27, Tatiana Gavrikova28, Philippe Barthelemy29, Avishay Sella30, Karim Fizazi31, Giulia Baciarello31, Jean-Marc Fererro32, Brigitte Laguerre33, Benjamin Verret1, Sophie Hans1, Stéphane Oudard34. 1. European Georges Pompidou Hospital, Paris, France. 2. Centre Armoricain d'Oncologie, CARIO, Plerin, France. 3. Alexandra Hospital, University of Athens, Athens, Greece; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Bergonie Institute, Bordeaux, France. 5. Istituto Oncologico Veneto Iov IRCCS, Padova, Italy. 6. Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK; University Hospitals of Morecombe Bay, NHS Foundation Trust, Lancaster, UK. 7. Royal Cornwall Hospitals NHS Trust, Truro, UK. 8. Medical university of Vienna, Vienna, Austria. 9. Institut de Cancérologie Lucien Neuwirth, Saint Priest en Jarez, France. 10. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. 11. Clinique Pasteur, Brest, France. 12. Copenhagen University Hospital, Copenhagen, Denmark. 13. University Hospitals Bristol NHS Foundation Trust, Bristol, UK. 14. Guy's and St. Thomas' Hospital NHS Trust, London, UK. 15. Santa Ciara Hospital, Trento, Italy. 16. Institut Curie, Paris, France. 17. Gentilly Oncology Centre, Nancy, France. 18. Jean Godinot Institute, Reims, France. 19. Centre Léon Bérard, Lyon, France. 20. Hôpital Cochin, Paris, France. 21. Hôpital d'Instruction des armées, Bégin, Saint Mandé, France. 22. Hull and East Yorkshire Hospitals NHS Trust, Hull, UK. 23. CHD Vendee-Hopital Les Oudairies, La Roche Sur Yon, France. 24. La Timone Hospital, Marseille, France. 25. CHU de Bordeaux, Bordeaux, France. 26. University Hospital Vall d'Hebron, Barcelona, Spain. 27. CHRU de Besançon, Besançon, France. 28. Centre Hospitalier de Sens, Sens, France. 29. Hôpital Civil, Strasbourg, France. 30. Assaf Harofeh Medical Centre, Zerifin, Israel. 31. Gustave Roussy, University of Paris Sud, Villejuif, France. 32. Centre Antoine Lacassagne, Nice, France. 33. Centre Eugène Marquis, Rennes, France. 34. European Georges Pompidou Hospital, Paris, France. Electronic address: stephane.oudard@aphp.fr.
Abstract
BACKGROUND: The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown. OBJECTIVE: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences. DESIGN, SETTING, AND PARTICIPANTS: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the prostate-specific antigen (PSA) response (decrease ≥50% from baseline) to each therapy. Secondary endpoints included best clinical benefit, time to PSA progression, radiological progression-free survival (rPFS), overall survival (OS), and toxicity. RESULTS AND LIMITATIONS: A total of 158 patients received DOC→CABA→ART (group 1), 456 received DOC→ART→CABA (group 2), and 55 received ART→DOC→CABA (group 3). At baseline, PSA progression only and Gleason <8 were more common in group 3. PSA response on DOC was lower in group 3 than in other groups (p=0.02) and PSA response on CABA was higher in the second than in the third line (p=0.001). In Group 3, rPFS on ART (6.6 mo) and DOC (9.2 mo) was also shorter than in the other groups. OS calculated from the first life-extending therapy reached 34.8, 35.8, and 28.9 mo in groups 1, 2 and 3, respectively (p=0.007). Toxicity was comparable between the arms. The main limitations of the trial are its retrospective design and the low number of patients in group 3. CONCLUSIONS: In this retrospective trial, sequencing of DOC, CABA, and one ART, was associated with median OS of up to 35.8 mo. CABA seemed to retain its activity regardless of treatment sequence. DOC activity after ART appeared to be reduced, but the data are insufficient to conclude that cross-resistance occurs. PATIENT SUMMARY: The order of drugs administered to patients with metastatic castration-resistant prostate cancer could impact their efficacy, with cabazitaxel appearing to retain its activity whatever the therapeutic sequence.
BACKGROUND: The optimal sequence of life-extending therapies in metastatic castration-resistant prostate cancer (mCRPC) is unknown. OBJECTIVE: To evaluate outcomes among mCRPC patients treated with docetaxel (DOC), cabazitaxel (CABA), and a novel androgen receptor-targeted agent (ART; abiraterone acetate or enzalutamide) according to three different sequences. DESIGN, SETTING, AND PARTICIPANTS: Data from 669 consecutive mCRPC patients were retrospectively collected between November 2012 and October 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the prostate-specific antigen (PSA) response (decrease ≥50% from baseline) to each therapy. Secondary endpoints included best clinical benefit, time to PSA progression, radiological progression-free survival (rPFS), overall survival (OS), and toxicity. RESULTS AND LIMITATIONS: A total of 158 patients received DOC→CABA→ART (group 1), 456 received DOC→ART→CABA (group 2), and 55 received ART→DOC→CABA (group 3). At baseline, PSA progression only and Gleason <8 were more common in group 3. PSA response on DOC was lower in group 3 than in other groups (p=0.02) and PSA response on CABA was higher in the second than in the third line (p=0.001). In Group 3, rPFS on ART (6.6 mo) and DOC (9.2 mo) was also shorter than in the other groups. OS calculated from the first life-extending therapy reached 34.8, 35.8, and 28.9 mo in groups 1, 2 and 3, respectively (p=0.007). Toxicity was comparable between the arms. The main limitations of the trial are its retrospective design and the low number of patients in group 3. CONCLUSIONS: In this retrospective trial, sequencing of DOC, CABA, and one ART, was associated with median OS of up to 35.8 mo. CABA seemed to retain its activity regardless of treatment sequence. DOC activity after ART appeared to be reduced, but the data are insufficient to conclude that cross-resistance occurs. PATIENT SUMMARY: The order of drugs administered to patients with metastatic castration-resistant prostate cancer could impact their efficacy, with cabazitaxel appearing to retain its activity whatever the therapeutic sequence.
Authors: Edmond M Kwan; Heidi Fettke; Megan Crumbaker; Maria M Docanto; Sarah Q To; Patricia Bukczynska; Andrew Mant; Nicole Ng; Siavash Foroughi; Lisa-Jane K Graham; Anne-Maree Haynes; Sarah Azer; Lisi Elizabeth Lim; Eva Segelov; Kate Mahon; Ian D Davis; Phillip Parente; Carmel Pezaro; Tilman Todenhöfer; Niranjan Sathianathen; Christine Hauser; Lisa G Horvath; Anthony M Joshua; Arun A Azad Journal: Transl Androl Urol Date: 2021-04
Authors: Heather Payne; Angus Robinson; Bernard Rappe; Serena Hilman; Ugo De Giorgi; Steven Joniau; Roberto Bordonaro; Stéphane Mallick; Louis-Marie Dourthe; Moisés Mira Flores; Josep Gumà; Benoit Baron; Aurea Duran; Alessandra Pranzo; Alexis Serikoff; David Mott; Mike Herdman; Marco Pavesi; Maria De Santis Journal: Int J Cancer Date: 2021-11-08 Impact factor: 7.316