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ORIGINAL ARTICLE |
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| Year : 2017 | Volume
: 33
| Issue : 4 | Page : 333-334 |
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A game changing LATITUDE: Role of abiraterone plus prednisolone in metastatic hormone-sensitive prostate cancer
Aditya Prakash Sharma
Department of Urology, Advance Urology Centre, PGIMER, Chandigarh, India
| Date of Submission | 12-Aug-2017 |
| Date of Acceptance | 29-Aug-2017 |
| Date of Web Publication | 27-Sep-2017 |
Correspondence Address:
Aditya Prakash Sharma
Department of Urology, Advance Urology Centre, PGIMER, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/iju.IJU_250_17
How to cite this article:
Sharma AP. A game changing LATITUDE: Role of abiraterone plus prednisolone in metastatic hormone-sensitive prostate cancer. Indian J Urol 2017;33:333-4 |
 Summary | |  |
The recently published LATITUDE trial is a multinational, multicenter, phase III randomized, double-blind, placebo-controlled study funded by Janssen Research and development.[1] It was presented in ASCO 2017 meeting and is published in the New England Journal of Medicine on June 4, 2017.[1] The study was designed to determine if newly diagnosed high-risk metastatic hormone-naive prostate cancer patients benefit from the addition of abiraterone and low-dose prednisone to androgen deprivation therapy (ADT).
The study, which commenced in 2013, has been terminated while conducting the interim analysis at median follow-up of 30.7 months. 1199 patients at 235 sites in 34 countries were randomized to receive ADT plus abiraterone (1000 mg daily) plus prednisone (5 mg daily) (Treatment arm-597 patients) or ADT plus dual placebos (Control arm-602 patients). Majority of the patients in each arm received Luteinizing Hormone-Releasing Hormone-based therapy. The two primary end-points were overall survival and radiographic progression free survival. The study found that the treatment arm had improvement in both overall survival and progression-free survival. In the treatment arm, the risk of death reduced by 38% compared to the control arm (hazard ratio [HR] = 0.62; 95% confidence interval (CI) [0.51–0.76], P < 0.0001) while risk reduction in terms of progression was 53% compared to placebo (HR = 0.47; 95% CI [0.39–0.55], P < 0.0001). The median overall survival was significantly longer in the treatment arm than in the control arm (not reached vs. 34.7 months) and median length of radiographic progression-free survival was 33.0 months in the treatment arm and 14.8 months in the control arm. This marked improvement came at the cost of higher complications, namely, hypertension and hypokalemia in the treatment arm. The authors attributed it to the use of lower dose of prednisolone (5 mg) as compared to the conventionally used dosage (10 mg) and longer duration of abiraterone therapy. Subsequent therapies were needed in 125 patients (21%) in the treatment arm and 246 (41%) in the placebo arm. Docetaxel was the most common postprogression treatment in both the groups.
| Comment | | |
The LATITUDE trial is a multinational study and included patients from 34 countries of various ethnicities.[1] They specifically included patients who were high risk (portending poor survival) with at least two of the 3 high-risk factors, namely, Gleason score of 8 or more, at least three bone lesions, and the presence of measurable visceral metastasis. This inclusion criteria were similar to other recent trials such as STAMPEDE and CHAARTED which evaluated the role of docetaxel therapy in metastatic prostate cancer patients.[2],[3] As difference for overall survival between the treatment arm and the control arm was significant at the time of the first interim analysis, the independent data and safety monitoring committee recommended unblinding the study and allowing for crossover from the control arm to the treatment arm. The analysis was considered to be final at the end of the interim analysis. The study mirrors the result of another recently published abiraterone arm of STAMPEDE trial which included 1917 patients and showed overall survival improvement of 37% (HR, 0.63; 95% CI [0.52–0.76], P < 0.001).[4]
After the STAMPEDE and CHAARTED trials which supported the role of docetaxel chemotherapy in metastatic hormone-naive prostate cancer, the LATITUDE trial may be a new practice changer.[1],[2],[3] The LATITUDE trial, together with the abiraterone arm of STAMPEDE trial, opens a new option for patients of metastatic prostate cancer.[1],[4] While docetaxel acts on cancer cells and is tumoricidal, abiraterone is an androgen biosynthesis inhibitor which is likely to be tumorostatic. However, active D4A metabolite of abiraterone has been found to have antitumor effects, plausibly due to blockade of multiple steroidogenic enzymes, and simultaneous androgen-receptor antagonism.[5] With increasing options becoming available for hormone-naive metastatic prostate cancer, clinicians shall have a multitude of options to offer to this subset of patients. What will be interesting is to know to choose between docetaxel and abiraterone? While on the one hand, docetaxel provides a potential curative treatment modality, on the other hand, abiraterone may provide similar survival rates to a subpopulation not fit for chemotherapy. A randomized head-to-head trial (PEACE-1 phase III trial, (ClinicalTrials.gov identifier: NCT01957436) looking into these two therapeutic arms may help identify the patient subset which is best fit for either of the treatments.
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
| References | | |
| 1. | Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 2017;377:352-60.  [ PUBMED] |
| 2. | Gandaglia G, Fossati N, Suardi N, Montorsi F, Briganti A. STAMPEDE trial and patients with non-metastatic prostate cancer. Lancet 2016;388:234-5. |
| 3. | Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015;373:737-46. [ PUBMED] |
| 4. | James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 2017;377:338-51. [ PUBMED] |
| 5. | Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, et al. Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature 2015;523:347-51. [ PUBMED] |
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