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6 december 2018: The Lancet

In The Lancet is deze maand het abstract van de SPARTAN studie met Apalutamide: Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial gepubliceerd. zie hieronder de resultaten. Het abstract staat onderaan dit artikel.

Dit studierapport: Recent trends in the management of advanced prostate cancer geeft een overzicht van de behandelingen bij prostaatkanker op dit moment d.d. 2018. Zie onderaan abstract van de studie en referentielijst

Table 1.

Summary of recent trials in castration-sensitive prostate cancer and non-metastatic (M0) castration-resistant prostate cancer.
TrialYearAgentPopulationPrimary endpointOutcome
summary
CHAARTED 2015 Docetaxel Castration-sensitive prostate
cancer (CSPC)
Overall survival (OS) 13.6-month
OS advantage
STAMPEDE 2016 Docetaxel CSPC OS 15.6-month
OS advantage
LATITUDE 2017 Abiraterone CSPC OS 7% 3-year
OS advantage
STAMPEDE 2017 Abiraterone CSPC OS 17% 3-year
OS advantage
SPARTAN 2018 Apalutamide M0 castration-resistant
prostate cancer (M0 CRPC)
Metastasis-free
survival (MFS)
24.3-month
MFS benefit
PROSPER 2018 Enzalutamide M0 CRPC MFS 21.9-month
MFS benefit

7 februari 2018: Bron: 2018 Genitourinary Cancers Symposium in San Francisco (Abstract 161).

Apalutamide in tabletvorm, een zogeheten CYP17 remmer zoals bv abiraterone, geeft 24,3 maanden langere ziektevrije tijd (72 procent) in vergelijking met een placebo bij patiënten met prostaatkanker  met een hoog risico op ziekteprogressie en uitzaaiingen door stijgende PSA waarden en hormoonresistentie. De onderzoekers van de fase III studie SPARTAN zijn enthousiast over deze resultaten omdat apaluzitamide weinig bijwerkingen geeft en blijkbaar toch weer wat anders werkt dan abiraterone, dat overigens 38 procent betere ziektevrije overleving gaf bij dezelfde groep van patiënten(zie: https://kanker-actueel.nl/abiraterone-acetate-zytiga-geeft-38-procent-minder-kans-op-overlijden-bij-nieuwe-diagnose-van-reeds-uitgezaaide-prostaatkanker-en-verdubbelt-progressievrije-ziekte-van-15-naar-33-maanden.html ) en enzalutamide, dat wel ook superieur was aan casodex / bicalutamide (zie o.a. https://kanker-actueel.nl/enzalutamide-is-ook-superieur-aan-bicalutamide-casodex-bij-prostaatkankerpatienten-ziektevrije-tijd-stijgt-mediaan-van-58-naar-157-maanden-psa-stijging-28-maanden-versus-nog-niet-bereikt-na-20-maanden.html.

Die wel goedgekeurd zijn bij uitgezaaide prostaatkanker maar nog niet bij niet-uitgezaaide prsotaatkanker. Apalutamide heeft hetzelfde werkingsmechanisme als enzalutamide maar heeft wel voordelen ten opzichte van enzalutamide door de lagere doses die nodig zijn, lees ook in Wikipedia

"Tot aan dit onderzoek waren er geen geneesmiddelen waarvan bewezen is dat ze echt een significante verbetering geven aan mannen met niet-uitgezaaide prostaatkanker, ondanks standaard hormonale therapie. Deze resultaten tonen aan dat apalutamide een significant verschil maakte in het verlengen van de tijd vóór de ontwikkeling van uitzaaiingen, "zegt hoofdonderzoeksauteur Eric J. Small, MD, FASCO, Professor of Medicine at the University of California, San Francisco. Ik wil daarbij de kanttekening maken dat er nog geen studieresultaten bekend zijn maar zoals eerder hierboven aangegeven ook enzalutamide en abiraterone geven veel betere resultaten dan casodex. Maar omdat er nog geen resultaten uit recente studies voorhanden zijn heeft de FDA deze ook nog geen goedkeuring gegeven voor deze groep van patiënten.

De FDA heeft voor deze groep van prostaatkankerpatiënten nog nooit een medicijn goedgekeurd, aldus de onderzoekers. Tekst gaat verder onder grafiek van CYP17 remmers en het werkingsmechanisme

Apalutamnide

In een eerdere fase II studie gaf apalutamide ook veel betere resultaten in vergelijking met bicalutamide (Casodex) (Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines.

Er is officieel nog geen abstract gepubliceerd van de SPARTAN studie maar wordt tijdens het 2018 Genitourinary Cancers Symposium gepresenteerd.

Kernpunten uit de studie uit het persbericht met de tussenresultaten zijn veelbelovend:

  • Apalutamide verlaagde het risico op uitzaaiingen en overlijden met 72% in vergelijking met placebo en verlengde de mediane uitzaaiingsvrije overleving met 2 jaar, dit is statistisch significant (40,5 maanden in de apalutamidegroep versus 16,2 maanden in de placebogroep).
  • Bij deze tussentijdse analyse voor de algehele overleving merkten onderzoekers ook een trend op ter verbetering van de algehele overleving voor mannen die apalutamide versus placebo kregen, hoewel het verschil (nog) niet statistisch significant was.

Hier een beschrijving van hoe de studie was opgezet:

The SPARTAN study was conducted at 332 institutions worldwide and enrolled 1,207 men. Patients with nonmetastatic castration-resistant prostate cancer who had stopped responding to ADT and were at high risk of metastasis based on a PSA doubling time of 10 months or less were randomly assigned to receive apalutamide or placebo taken as daily tablets, added to ongoing ADT. At the time of development of metastases, patients were treated with standard second therapies at their physician’s discretion and had an option to receive on-study abiraterone acetate (Zytiga) and prednisone, a standard of care.

The median PSA doubling time at study entry was approximately 4.5 months in both the apalutamide and placebo groups.

Apalutamide was well tolerated, with 10.7% of men discontinuing treatment due to adverse events compared with 6.3% of men receiving placebo. Quality-of-life scores were maintained in those men receiving apalutamide added to ADT.

Zodra het abstract of volledige studierapprot beschikbaar is zal ik dat erbij plaatsen.

patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL

2018 Oct;19(10):1404-1416. doi: 10.1016/S1470-2045(18)30456-X. Epub 2018 Sep 10.

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial.

Abstract

BACKGROUND:

In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL).

METHODS:

SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204.

FINDINGS:

Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8-26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group.

INTERPRETATION:

In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL.

FUNDING:

Janssen Research & Development.

we review the most recent studies leading to these significant changes in the treatment of advanced prostate cancer

Table 1.

Summary of recent trials in castration-sensitive prostate cancer and non-metastatic (M0) castration-resistant prostate cancer.
TrialYearAgentPopulationPrimary endpointOutcome
summary
CHAARTED 2015 Docetaxel Castration-sensitive prostate
cancer (CSPC)
Overall survival (OS) 13.6-month
OS advantage
STAMPEDE 2016 Docetaxel CSPC OS 15.6-month
OS advantage
LATITUDE 2017 Abiraterone CSPC OS 7% 3-year
OS advantage
STAMPEDE 2017 Abiraterone CSPC OS 17% 3-year
OS advantage
SPARTAN 2018 Apalutamide M0 castration-resistant
prostate cancer (M0 CRPC)
Metastasis-free
survival (MFS)
24.3-month
MFS benefit
PROSPER 2018 Enzalutamide M0 CRPC MFS 21.9-month
MFS benefit
Version 1. . 2018; 7: F1000 Faculty Rev-1513.
Published online 2018 Sep 21. doi:  [10.12688/f1000research.15382.1]
PMCID: PMC6173112
PMID: 30345007

Recent trends in the management of advanced prostate cancer

Chad Ritch, Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing1 and Michael Cookson, Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editinga,2

Abstract

Advanced prostate cancer includes a wide spectrum of disease ranging from hormone naïve or hormone sensitive to castration resistant, both containing populations of men who have demonstrable metastatic and non-metastatic states. The mainstay of treatment for metastatic hormone-sensitive prostate cancer is androgen deprivation therapy (ADT). However, recent level 1 evidence demonstrates that the addition of chemotherapy or abiraterone acetate to ADT results in significant survival advantage as compared with ADT alone. Furthermore, in non-metastatic castration-resistant prostate cancer (M0 CRPC), two second-generation anti-androgens, apalutamide and enzalutamide, when used in combination with ADT, have demonstrated a significant benefit in metastasis-free survival. Here, we review the most recent studies leading to these significant changes in the treatment of advanced prostate cancer.

Conclusions

There have been significant recent strides in the management of advanced prostate cancer. Major changes in the treatment of hormone-sensitive disease have occurred on the basis of level 1 evidence to support upfront use of docetaxel plus ADT and in addition the use of androgen annihilation with abiraterone acetate plus prednisone in combination with ADT. Also, in the M0 CRPC state, there are now two randomized trials demonstrating improved MFS with the addition of apalutamide or enzalutamide in combination with ADT for patients at high risk for metastases. PARP inhibitors and immunotherapeutic agents such as CTLA-4 inhibitors are also being studied and may become a part of the treatment armamentarium in the near future.

The referees who approved this article are:

  • Axel Heidenreich, Klinik für Urologie, Uro-Onkologie, Roboter-assistierte und Spezielle Urologische Chirurgie, Universitätsklinikum Köln, Köln, Germany
    No competing interests were disclosed.
  • Alicia K Morgans, Division of Hematology/Oncology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Competing interests: Consulting honoraria from Janssen, Sanofi, Bayer, Genentech, and Astra Zeneca.
  • Christopher B Anderson, Department of Urology, Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York, USA
    No competing interests were disclosed.

References

1. Li J, Siegel DA, King JB: Stage-specific incidence rates and trends of prostate cancer by age, race, and ethnicity, United States, 2004-2014. Ann Epidemiol. 2018;28(5):328–30. 10.1016/j.annepidem.2018.03.001 [PMC free article] [PubMed] [CrossRef]
2. Steele CB, Li J, Huang B, et al. : Prostate cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017;123 Suppl 24:5160–77. 10.1002/cncr.31026 [PMC free article] [PubMed] [CrossRef]
3. Marques RB, Dits NF, Erkens-Schulze S, et al. : Bypass mechanisms of the androgen receptor pathway in therapy-resistant prostate cancer cell models. PLoS One. 2010;5(10):e13500. 10.1371/journal.pone.0013500 [PMC free article] [PubMed] [CrossRef]
4. Harris WP, Mostaghel EA, Nelson PS, et al. : Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6(2):76–85. 10.1038/ncpuro1296 [PMC free article] [PubMed] [CrossRef]
5. Huggins C, Hodges CV: Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22(4):232–40. 10.3322/canjclin.22.4.232 [PubMed] [CrossRef]
6. Patrikidou A, Loriot Y, Eymard JC, et al. : Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17(4):348–52. 10.1038/pcan.2014.35 [PubMed] [CrossRef]
7. Omlin A, Pezaro C, Mukherji D, et al. : Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms. Eur Urol. 2013;64(2):300–6. 10.1016/j.eururo.2012.12.029 [PubMed] [CrossRef]
8. Tannock IF, de Wit R, Berry WR, et al. : Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12. 10.1056/NEJMoa040720 [PubMed] [CrossRef] F1000 Recommendation
9. Petrylak DP, Tangen CM, Hussain MH, et al. : Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20. 10.1056/NEJMoa041318 [PubMed] [CrossRef] F1000 Recommendation
10. Sweeney CJ, Chen YH, Carducci M, et al. : Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737–46. 10.1056/NEJMoa1503747 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
11. James ND, Sydes MR, Clarke NW, et al. : Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–77. 10.1016/S0140-6736(15)01037-5 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
12. Fizazi K, Tran N, Fein L, et al. : Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352–60. 10.1056/NEJMoa1704174 [PubMed] [CrossRef] F1000 Recommendation
13. James ND, de Bono JS, Spears MR, et al. : Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338–51. 10.1056/NEJMoa1702900 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
14. Kantoff PW, Higano CS, Shore ND, et al. : Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22. 10.1056/NEJMoa1001294 [PubMed] [CrossRef] F1000 Recommendation
15. de Bono JS, Logothetis CJ, Molina A, et al. : Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005. 10.1056/NEJMoa1014618 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
16. Ryan CJ, Smith MR, Fizazi K, et al. : Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152–60. 10.1016/S1470-2045(14)71205-7 [PubMed] [CrossRef]
17. Scher HI, Fizazi K, Saad F, et al. : Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97. 10.1056/NEJMoa1207506 [PubMed] [CrossRef] F1000 Recommendation
18. Beer TM, Armstrong AJ, Rathkopf DE, et al. : Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33. 10.1056/NEJMoa1405095 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
19. de Bono JS, Oudard S, Ozguroglu M, et al. : Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54. 10.1016/S0140-6736(10)61389-X [PubMed] [CrossRef] F1000 Recommendation
20. Parker C, Nilsson S, Heinrich D, et al. : Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23. 10.1056/NEJMoa1213755 [PubMed] [CrossRef] F1000 Recommendation
21. Smith MR, Saad F, Chowdhury S, et al. : Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378(15):1408–18. 10.1056/NEJMoa1715546 [PubMed] [CrossRef] F1000 Recommendation
22. Hussain M, Fizazi K, Saad F, et al. : PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol. 2018;36(6_suppl):3 10.1200/JCO.2018.36.6_suppl.3 [CrossRef]
23. Gravis G, Fizazi K, Joly F, et al. : Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(2):149–58. 10.1016/S1470-2045(12)70560-0 [PubMed] [CrossRef]
24. Sydes MR, Spears MR, Mason MD, et al. : Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29(5):1235–48. 10.1093/annonc/mdy072 [PMC free article] [PubMed] [CrossRef]
25. Scher HI, Morris MJ, Stadler WM, et al. : Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402–18. 10.1200/JCO.2015.64.2702 [PMC free article] [PubMed] [CrossRef]
26. Hirst CJ, Cabrera C, Kirby M: Epidemiology of castration resistant prostate cancer: a longitudinal analysis using a UK primary care database. Cancer Epidemiol. 2012;36(6):e349-53. 10.1016/j.canep.2012.07.012 [PubMed] [CrossRef]
27. Smith MR, Kabbinavar F, Saad F, et al. : Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918–25. 10.1200/JCO.2005.01.529 [PubMed] [CrossRef]
28. Cookson MS, Lowrance WT, Murad MH, et al. : Castration-resistant prostate cancer: AUA guideline amendment. J Urol. 2015;193(2):491–9. 10.1016/j.juro.2014.10.104 [PubMed] [CrossRef]
29. Cookson MS, Roth BJ, Dahm P, et al. : Castration-resistant prostate cancer: AUA Guideline. J Urol. 2013;190(2):429–38. 10.1016/j.juro.2013.05.005 [PubMed] [CrossRef]
30. Penson DF, Armstrong AJ, Concepcion R, et al. : Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016;34(18):2098–106. 10.1200/JCO.2015.64.9285 [PubMed] [CrossRef]
31. Hussain M, Fizazi K, Saad F, et al. : Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018;378(26):2465–74. 10.1056/NEJMoa1800536 [PubMed] [CrossRef] F1000 Recommendation
32. Pritchard CC, Mateo J, Walsh MF, et al. : Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016;375(5):443–53. 10.1056/NEJMoa1603144 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
33. Fong PC, Boss DS, Yap TA, et al. : Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34. 10.1056/NEJMoa0900212 [PubMed] [CrossRef] F1000 Recommendation
34. Mateo J, Carreira S, Sandhu S, et al. : DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015;373(18):1697–708. 10.1056/NEJMoa1506859 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation
35. Clarke N, Wiechno P, Alekseev B, et al. : Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018;19(7):975–86. 10.1016/S1470-2045(18)30365-6 [PubMed] [CrossRef]
36. Carosella ED, Ploussard G, LeMaoult J, et al. : A Systematic Review of Immunotherapy in Urologic Cancer: Evolving Roles for Targeting of CTLA-4, PD-1/PD-L1, and HLA-G. Eur Urol. 2015;68(2):267–79. 10.1016/j.eururo.2015.02.032 [PubMed] [CrossRef]
37. Kwon ED, Drake CG, Scher HI, et al. : Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12. 10.1016/S1470-2045(14)70189-5 [PMC free article] [PubMed] [CrossRef] F1000 Recommendation

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