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UROSCAN |
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| Year : 2021 | Volume
: 37
| Issue : 3 | Page : 288-290 |
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Docetaxel, abiraterone, enzalutamide, apalutamide in patients with metastatic hormone-sensitive prostate cancer
Harkirat Singh Talwar
Department of Urology, AIIMS, Rishikesh, Uttarakhand, India
| Date of Submission | 06-Oct-2020 |
| Date of Decision | 20-Mar-2021 |
| Date of Acceptance | 08-May-2021 |
| Date of Web Publication | 1-Jul-2021 |
Correspondence Address:
Harkirat Singh Talwar
Department of Urology, AIIMS, Rishikesh, Uttarakhand
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/iju.IJU_547_20
How to cite this article:
Talwar HS. Docetaxel, abiraterone, enzalutamide, apalutamide in patients with metastatic hormone-sensitive prostate cancer. Indian J Urol 2021;37:288-90 |
 Summary | |  |
Sathianathen et al.[1] in their systematic review and network meta-analysis, published in the European Urology 2020, compared the efficacy of combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC) using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in addition to androgen deprivation therapy (ADT).
A network meta-analysis is a statistical method to compare the indirect evidence of multiple treatment options when a direct head to head comparison is lacking. This is different from a meta-analysis which combines data of several studies comparing the same treatments.[2] The objective of this network meta-analysis was to prove the superiority of one of the combination approach over the other, as head-to-head trials are currently unavailable. The primary end point of the study was to compare the overall survival (OS), and progression-free survival was the secondary outcome. A subgroup analysis was also performed to assess the efficacy of these drugs in high and low-volume disease settings, respectively.
Seven trials including three for docetaxel (GETUG-AFU 15, CHAARTED, and STAMPEDE), two for abiraterone (STAMPEDE and LATITUDE), and one each for enzalutamide (ENZAMET) and apalutamide (TITAN) were included in this network meta-analysis. In all these trials, the combination therapy in question was shown to be superior to ADT alone in terms of OS. Indirect comparisons between the combination therapies showed that all four therapies were statistically comparable with respect to OS; however, enzalutamide + ADT had the least hazard ratio (HR) and was superior in delaying death (HR for enzalutamide + ADT 0.53, 95% confidence interval [CI] 0.37–0.75; apalutamide 0.64, 95% CI 0.47–0.86; abiraterone 0.69, 95% CI 0.61–0.79; docetaxel 0.81, 95% CI 0.72–0.92). HR is defined as the chance of an event occurring in the treatment arm divided by the chance of the event occurring in the control arm. In the present comparative survival analysis, the drug with the least HR was the one that was the best in delaying death. Surface under the cumulative ranking curve (SUCRA) was used to rank the preference of each treatment, which showed that enzalutamide had a 76.9% probability of being the preferred drug followed by apalutamide with a 19.8% probability. SUCRA is a graphical representation to rank the various treatment options in a network analysis from the highest to lowest in the order of their efficacy. Each treatment option is given a number from 0 to 100. The higher the number, the higher is its efficacy and probability of being in one of the top ranks and vice versa.[2]
Subgroup analysis revealed that only enzalutamide had a superior OS as compared to ADT and had the least overall HR (0.38, 95% CI 0.20–0.68) for low-volume disease. For high-volume disease, although enzalutamide had the least HR (0.62, 95% CI 0.40–0.95), no drug was statistically superior to the other in the terms of OS. SUCRA analysis ranked enzalutamide as the best, with 84.2% and 54.4% probability in the low-volume and the high-volume disease, respectively. In terms of overall progression-free analysis, although all the four drugs delayed progression as compared to ADT, enzalutamide and abiraterone were the preferred drugs over docetaxel and apalutamide. Thus, it could be concluded that although all the four drugs are statistically comparable in the terms of OS for mHSPC, enzalutamide was better than the other three in the terms of HRs, more so for the low-volume disease.
| Comment | | |
Over the last decade, several drugs have been added to the repertoire of an uro-oncologist treating mHSPC. All the latest guidelines acknowledge that a combination therapy with ADT is better than ADT alone in improving the OS. The EAU guidelines strongly recommend offering ADT combined with either docetaxel, abiraterone, enzalutamide, or apalutamide to patients with treatment naive M1 disease, who are fit to receive the respective drugs.[3] However, the question remains as to which is the best treatment option and how do we choose one? Several factors that influence this decision include patient preference, performance status, side effect profile, high versus low volume/risk, mode of administration, duration of treatment, availability, and cost.[4] Currently, no randomized controlled trial exists to prove the outright superiority of one drug over the other, and a personalized approach to treatment is the best bet. By virtue of being the first drug to be used and with the maximum evidence, docetaxel seems to be the preferred drug by most of the physicians in high-volume disease, especially in the Indian setting. The advantages of using docetaxel include fixed dosing, maximum cost–benefit ratio, better performance status at this treatment-naive stage, better response in poorly differentiated tumors, and saving the other drugs for when docetaxel fails. However, when it comes to low-volume disease, docetaxel has not shown an OS benefit and thus is not favored.[5]
The current network meta-analysis analyzed all the landmark studies of the aforementioned four drugs and showed that enzalutamide was better at delaying death as compared to its direct competitors, especially in the low-volume disease setting.[1] Advantages with enzalutamide include a very good quality-adjusted survival (cf. docetaxel) and a clear advantage of avoiding additional steroids (cf. abiraterone). However, enzalutamide needs to be avoided in patients with peripheral neuropathy or seizures and, as opposed to docetaxel, may not be a cost-effective option.[6] Thus, future trials are needed to out rightly declare one drug as the clear winner, and till future evidence is available, a tailored treatment with a personalized approach is required in men with carcinoma prostate presenting with metastatic disease [Table 1]. | Table 1: Comparing the advantages of disadvantages of using docetaxel, abiraterone, enzalutamide, and apalutamide in metastatic hormone-sensitive prostate cancer
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The current article was a well-performed review assessing the efficacy of various combination approaches in mHSPC. The authors did address the research question by taking into account seven trials, all of which were landmark studies of the respective drugs in question, including three for docetaxel (GETUG-AFU 15, CHAARTED, and STAMPEDE), two for abiraterone (STAMPEDE and LATITUDE), and one each for enzalutamide (ENZAMET) and apalutamide (TITAN). The authors concluded that all four drugs were statistically comparable in the terms of OS for mHSPC, although enzalutamide was better than the other three in terms of HR and could hold a promising future in the treatment paradigm of metastatic prostate cancer.
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
| References | | |
| 1. | Sathianathen NJ, Koschel S, Thangasamy IA, Teh J, Alghazo O, Butcher G, et al. Indirect comparisons of efficacy between combination approaches in metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis. Eur Urol 2020;77:365-72.  |
| 2. | Rücker G, Schwarzer G. Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol 2015;15:58. |
| 3. | Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cornford P, et al. Members of the EAU – ESTRO – ESUR –SIOG Prostate Cancer Guidelines Panel. EAU – ESTRO – ESUR – SIOG Guidelines on Prostate Cancer. Edn. Presented at the EAU Annual Congress Amsterdam. Arnhem, The Netherlands: EAU Guidelines Office; 2020. |
| 4. | Shore ND, Antonarakis ES, Cookson MS, Crawford ED, Morgans AK, Albala DM, et al. Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines. Prostate 2020;80:527-44. |
| 5. | Sharma AP, Mavuduru RS, Bora GS, Devana SK, Singh SK, Mandal AK. STAMPEDEing metastatic prostate cancer: CHAARTing the LATITUDEs. Indian J Urol 2018;34:180-4. [ PUBMED] [Full text] |
| 6. | Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 2019;381:121-31. |
[Table 1]
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