|Ahead of print publication
Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic hormone-sensitive prostate cancer in Indian population
Alok Gupta1, Shaik Maheboob Hussain1, Neha Sonthwal2, Harit Chaturvedi3
1 Department of Medical Oncology, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
2 Department of Clinical Research, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
3 Department of Surgical Oncology, Max Institute of Cancer Care, Max Super Specialty Hospital, New Delhi, India
|Date of Submission||17-May-2019|
|Date of Decision||26-Aug-2019|
|Date of Acceptance||26-Nov-2019|
|Date of Web Publication||09-Oct-2020|
Departments of Medical Oncology, Max Institute of Cancer Care, Max Super Specialty Hospital, Saket, New Delhi - 110 017
Source of Support: None, Conflict of Interest: None
Background: The addition of docetaxel or abiraterone to androgen deprivation therapy (ADT) achieves superior survival outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) in predominantly Western population. We sought to evaluate the treatment outcomes of adding docetaxel or abiraterone to ADT in Indian population.
Methods: We reviewed the medical records of ninety patients with newly diagnosed mHSPC who received treatment between January 2015 and June 2018. Patients received ADT alone or ADT + docetaxel or ADT + abiraterone as initial treatment. Monthly clinical evaluation and prostate-specific antigen (PSA) measurement were done. Outcome measures analyzed included PSA decline <90%, serological complete response (sCR) (PSA <0.2 ng/ml), and progression to CRPC. Outcome variable was compared using Fisher's exact test.
Results: Patients received ADT alone (n = 37) or ADT + docetaxel (n = 31) or ADT + abiraterone (n = 22). The median age was 67.5 years (range, 41–87 years) and the median PSA was 88.5 ng/ml (range, 1.12–4000). PSA decline <90% was seen in 22 (73%), 24 (86%), and 17 (94%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. sCR was achieved in 5 (17%), 10 (36%), and 9 (50%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. Progression to CRPC was observed in 18 (60%), 11 (39%), and 2 (11%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups.
Conclusion: The addition of docetaxel or abiraterone to ADT achieves a deeper serological response and reduces progression to CRPC compared to ADT alone in mHSPC patients of Indian origin. Longer follow-up is required to comment on overall survival and also to determine which combination (ADT + docetaxel or ADT + abiraterone) is superior to others, if at all.
Keywords: Abiraterone, docetaxel, metastatic hormone-sensitive prostate cancer
|How to cite this URL:|
Gupta A, Hussain SM, Sonthwal N, Chaturvedi H. Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic hormone-sensitive prostate cancer in Indian population. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 26]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=297620
| > Introduction|| |
Androgen deprivation therapy (ADT) has been the mainstay of treatment in metastatic hormone-sensitive prostate cancer (mHSPC) for over 75 years. In recent years, two important advances have changed the management algorithm of patients with mHSPC. The first was the addition of upfront chemotherapy to ADT. The benefit of chemohormonal approach, where docetaxel was added to ADT, showed unprecedented improvement in overall survival (OS), especially in high-volume metastatic disease.,, The second practice-changing development was the addition of upfront abiraterone to ADT in high-risk mHSPC, which also resulted in significant improvement in OS. Such improvement came with an acceptable price in terms of toxicity, which would be expected from chemotherapy or an endocrine therapy, necessitating comparison of these combination treatments.
However, the comparative efficacy of ADT alone, ADT + docetaxel, and ADT + abiraterone in Indian patients with mHSPC remains to be established. As there are no published studies from India which directly compare these treatment options, we conducted the present study to compare serological outcomes in the above-mentioned groups.
| > Methods|| |
We retrospectively reviewed the prospectively kept medical records of metastatic prostate cancer patients treated at our center between January 2015 and June 2018. Ninety patients with newly diagnosed mHSPC were found eligible for the study. Diagnosis was established by transrectal ultrasound-guided prostate biopsy, and staging was done by Ga68 prostate-specific membrane antigen (PSMA) positron emission tomography–computed tomography (PET-CT) scan in all the patients. Seventy-six patients with at least 6-month follow-up were included in outcome analysis.
Treatment and evaluation
All the patients received ADT as initial therapy. ADT consisted of a medical (luteinizing hormone-releasing hormone [LHRH] agonist of LHRH antagonist) or surgical castration (bilateral orchiectomy). Patients who were unfit for combination therapy received ADT alone. Patients diagnosed before June 2017 and fit to receive chemohormonal therapy received ADT + docetaxel (75 mg/m2 every 3 weekly for 6 doses). Patients diagnosed after June 2017 and fit to receive combination received either ADT + docetaxel (75 mg/m2 every 3 weekly for 6 doses) or ADT + abiraterone (1000 mg with prednisone 5 mg once daily by mouth), based on a shared decision-making between physician and patient. Demographics, clinic-pathological characteristics, radiological characteristics, and treatment received were systematically recorded. Monthly clinical evaluation and prostate-specific antigen (PSA) measurement were done. Imaging with Ga68 PSMA PET-CT scan was done at the time of documented castration resistance or as clinically indicated. Outcome measures analyzed included PSA decline <90%, serological complete response (sCR), and progression to CRPC. sCR was defined as PSA level <0.2 ng/mL. PSA progression was defined according to the Prostate Cancer Clinical Trials Working Group. The time to CRPC was defined as the time until documented clinical or serologic progression with a testosterone level of <50 ng/deciliter.
For analysis, patients were divided into three groups – ADT alone, ADT + docetaxel, and ADT + abiraterone. Baseline characteristics were recorded and compared between the three treatment groups. Serological response rates including sCR and progression to CRPC were compared with the use of Fisher's exact test. All statistical analyses were performed using SPSS software version 16.0. All reported P values were two-sided and considered statistically significant at P < 0.05.
| > Results|| |
The baseline characteristics are shown in [Table 1]. Thirty-seven patients received ADT alone, 31 patients received ADT + docetaxel, and 22 patients received ADT + abiraterone. The median age was 67.5 years (range, 41–87 years) and the median PSA was 88.5 ng/ml (range, 1.12–4000). The Gleason score was ≥8 in 57%, 71%, and 77% of the patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups. Bone and visceral metastases were present in 62% and 24%, 74% and 26%, 68% and 23% of the patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups, respectively.
The serological outcome analysis is shown in [Table 2]. PSA decline <90% was noted in 22 (73.3%), 24 (85.7%), and 17 (94.4%) in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups, respectively. sCR was achieved in 5 (17%), 10 (36%), and 9 (50%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups, respectively. Progression to CRPC was seen in 18 (60%), 11 (39.3%), and 2 (11.1%) patients in the ADT alone, ADT + docetaxel, and ADT + abiraterone groups, respectively.
| > Discussion|| |
In this study, real-world data of Indian men with newly diagnosed mHSPC treated either with ADT alone, ADT + docetaxel, or ADT + abiraterone were analyzed. One single-centric single-arm study recruited 40 metastatic prostate cancer patients who received initial ADT alone for 6–12 months and still had a PSA level higher than 4.0 ng/mL. The study highlighted delaying the introduction of abiraterone with ADT compromises treatment efficacy. The primary endpoint was the rate of a PSA level of 0.2 ng/mL or lower within 12 months of starting abiraterone. This study did not meet its primary endpoint that was 13%. In our study, 16.7% of the patients achieved sCR in the ADT alone group and 35.7% in the ADT + docetaxel group which is comparable to 16.8% and 27.7% sCR in the CHAARTED trial ADT alone and ADT + docetaxel arms, respectively. The improvement in OS correlated with the increased attainment of a PSA level lower than 0.2 ng/mL, further validating the relevance of this endpoint. Serological outcome was found better in the abiraterone group as <90% PSA decline was achieved in 94.4% of the patients and sCR was achieved in 50% of the patients. In comparison, among patients who received ADT + docetaxel, <90% PSA decline was achieved in 85.7% of the patients, whereas sCR was achieved in 35.7% of the patients. A significant difference (P = 0.0037) was noted among the percentage of patients who had progressed to CRPC, least being in the abiraterone group (11.1%), followed by docetaxel group (39.3%), followed by ADT alone group (60%).
Although serological outcomes are in favor of abiraterone in our study, longer follow-up is required for data to be correlated as to know which agent has better outcomes in this ethnicity and set of patients. With no data on the direct comparison of abiraterone and docetaxel, our study thus tried to answer the optimal treatment in the management of metastatic castration-naive prostate cancer. Indirect comparison of abiraterone and docetaxel on the basis of results from the LATITUDE and STAMPEDE trials reported similar survival benefit, of reduction in risk of death, by 38% and 39%, respectively, with abiraterone and docetaxel. However, the other parameters favor abiraterone in the management, with abiraterone prolonging progression-free survival and reducing the risk of failure-free survival by 69% as compared to 39% by docetaxel. This effect of abiraterone was explained by its direct effect on the PSA transcription as compared to cytotoxic chemotherapy like docetaxel which has an indirect effect on PSA production. The STOPCAP trial highlighted the indirect comparison of abiraterone and docetaxel with ADT on OS of patients. The result suggested abiraterone as a better and effective treatment option for both OS and failure-free survival (FFS) as compared to docetaxel with 94% OS probability and 100% FFS probability. The PEACE1 trial looking into these two therapeutic arms shall identify the patient subset which is the best fit for either of the treatments will help address the question of whether the benefits seen with docetaxel are overlapping or additional to those seen with that of abiraterone. Such studies were needed to be done in this set of patients.
| > Conclusion|| |
This study is limited by the fact that the follow-up of patients is short. A longer follow-up is required to determine the impact of deeper serological responses on OS. In conclusion, the addition of docetaxel or abiraterone to ADT in mHSPC increases the likelihood of achieving a deeper serological response, more importantly a sCR, and delays progression to CRPC state in Indian population. Whether it translates into improvement in OS, as in Western population, remains to be established.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]