[2021 ASCO] The importance of early new endocrine therapy for mHSPC patients from the TITAN study on the quality of life of patients

*For medical professionals' reference only, the 2021 American Society of Clinical Oncology Annual Meeting (ASCO 2021) will be held online from June 4 to 8, 2021
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As one of the largest and largest audiences in oncology, the ASCO annual meeting will show scholars from all walks of life the latest cutting-edge developments.
The conference announced a number of blockbuster research results in the field of urinary oncology
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This article will share the most important data in the field of prostate cancer: the patient quality of life (HRQoL) results finally analyzed by the TITAN study, and invited Professor Wang Junqi from the Affiliated Hospital of Xuzhou Medical University to give an in-depth interpretation
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The TITAN study is a multi-center, randomized, double-blind, controlled, prospective global phase III clinical study, which aims to explore the treatment of apatamide + ADT and placebo (PBO) + ADT in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) Efficacy and safety of patients (Figure 1)
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The study included a variety of patient types, high tumor burden, low tumor burden, localized disease stage received treatment (local treatment or systemic treatment), M1 stage received ≤6 cycles of docetaxel chemotherapy or ≤6 months All ADT treatments can be included in the group
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Of the 1052 mHSPC patients included in the study, 94 of them were Chinese patients.
They were randomized 1:1 to receive ADT combined with apatamide (240 mg qd) or placebo.
The main endpoints of the study are overall survival (OS) and imaging.
Progressive survival (rPFS)
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Figure 1.
TITAN study design The final analysis results of the TITAN study showed that apatamide significantly prolonged OS: The final analysis results of the efficacy and safety of the TITAN study were officially published in the Journal of Clinical Oncology (JCO) in May this year [1]
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The results showed that when the median follow-up time was 44 months, the overall median treatment time of the apatamide group and the placebo group were 39.
3 months and 20.
2 months, respectively.
The bit time is 15.
4 months
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Compared with placebo, apatamide can significantly reduce the risk of death by 35%, and the 4-year survival rates are 65% and 52%, respectively (Figure 2)
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Figure 2.
In the final TITAN analysis, the OS benefit of apatamide compared to the control group.
After the first interim analysis, about 40% of patients in the placebo group were crossed into the apatamide group when the label was opened.
After excluding the influence of cross-entry factors through the inverse probability censorship weighting (IPCW) method, apatamide can reduce the death risk of mHSPC patients by 48% (Figure 3)
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Figure 3.
After excluding the effect of cross-entry, the OS benefit of apatamide compared to the control group.
The median rate of 11.
4 months for mHSPC patients treated with ADT progressed to metastatic castration-resistant prostate cancer (mCRPC).
The median value of the apatamide group has not yet been reached, and apatamide can significantly reduce the risk of castration resistance by 76% in patients (Figure 4)
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Figure 4.
The time to CRPC benefit of apatamide compared to the control group.
The final analysis results of the TITAN study show that apatamide + ADT can significantly improve the OS of mHSPC patients, and the effect is very significant
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So, long-term use of apatamide + ADT treatment, will patients be troubled by adverse reactions? What is the patient's quality of life? TITAN study final analysis of patient quality of life report: The interim analysis of the TITAN study assessed the patient’s quality of life
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The results showed that with a median follow-up of 22.
7 months, compared with ADT alone, apatamide + ADT significantly improved the survival of patients, including rPFS and OS, while maintaining a high quality of life for patients, especially in severe pain.
The degree of pain and pain interference in the patamide group was less than that of the placebo group (Figure 5) [2]
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After the interim analysis, 40% of patients in the placebo group crossed over to the apatamide+ADT group to receive apatamide
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Figure 5.
TITAN study interim analysis of patients’ quality of life pain and evaluation of pain interference.
At this year’s ASCO conference, the results of the TITAN study’s final analysis of patients’ quality of life were announced [3]
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The quality of life of patients in this study was assessed using BPI-SF (Brief Pain Assessment), BFI (Fatigue Assessment) and FACT-P (Functional Assessment of Prostate Cancer Quality) scales
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The following are the baseline conditions of the patients (Table 1): Table 1.
The results of the final analysis of the baseline quality of life assessment of patients in the TITAN study showed that at a median follow-up of 44 months, >86% of patients in the apatamide+ADT group did not receive Or only suffer from a little adverse reaction-related trouble, the proportion is similar to that of the placebo+ADT group; >78% of the patients in the apatamide+ADT group have the same or improved physical fitness compared to baseline, while the placebo group is only >71% (Figure 6)
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The results indicate that patients receiving long-term apatamide + ADT treatment, most patients will not suffer or only suffer from a little adverse reaction, and physical fitness can still be maintained or even improved
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Figure 6.
Patients suffering from adverse reactions and assessment of physical fitness in the TITAN study.
The overall FACT-P assessment results show that patients with long-term use of apatamide + ADT can still maintain the same quality of life as the baseline, including physical fitness, mood, and physical fitness.
Function, social interaction, etc.
(Figure 7)
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Figure 7.
FACT-P results of the final analysis of the TITAN study.
The BPI-SF evaluation results show that the patient's pain intensity and pain interference scores remain stable over time (Figure 8)
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Figure 8.
BPI assessment of the final analysis of the TITAN study.
The above results further illustrate that long-term use of apatamide + ADT treatment can significantly improve patient survival and enable patients to have a high-quality life
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 Experts comment that in recent years, more and more combination treatments based on ADT have emerged in the mHSPC stage, including docetaxel chemotherapy and new endocrine therapies represented by abiraterone and apatamide [4-6 ], these programs can significantly delay the progress of the patient, thereby prolonging the overall survival of the patient
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Because the treatment of docetaxel and abiraterone is limited to patients with high tumor burden and newly diagnosed high-risk mHSPC respectively; for a wider range of mHSPC patients, there is still a lack of more aggressive treatment options
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 The phase III TITAN study of apatamide included a wide range of mHSPC patient types, including high tumor burden, low tumor burden, high-risk, low-risk, progression after treatment at the newly diagnosed or localized disease stage, and even mHSPC stage.
≤6 cycles of docetaxel chemotherapy can be included in the group, which is in line with the complex source and type of patients in the real world [6]
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Therefore, when the data of the TITAN study was first announced at the 2019 ASCO conference, it received extensive attention from clinicians [8]
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In the first interim analysis, compared with ADT alone, apatamide combined with ADT treatment can significantly reduce the overall risk of death of mHSPC patients by 33%, and the risk of imaging progression or death by 52%.
Prostate-specific antigen ( PSA) The risk of progress is reduced by 74%
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Although the median follow-up time is only 22.
3 months, the long-term benefits of apatamide are already very clear.
Therefore, mHSPC indications were approved in the United States and China in 2019 and 2020, respectively
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This year’s ASCO-GU announced the final analysis results of the TITAN study.
After nearly 4 years of follow-up, compared with ADT alone, apatamide combined with ADT can significantly reduce the risk of death by 35%, and the 4-year survival rate was respectively It is 65% and 52%, OS is 52.
2 months and not reached (P<0.
0001) [1,6]
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However, since apatamide showed excellent efficacy in the first interim analysis, 40% of the placebo group patients were crossed into the group to receive apatamide treatment[1]; if crossed into the group After the factors were excluded, the median survival time of mHSPC patients who received ADT alone was only 39.
8 months, suggesting that this type of patients should be actively intervened as soon as possible regardless of the tumor burden; and the combination therapy of apatamide can significantly reduce The risk of death is as high as 48% [1], which is very shocking data and far superior to the results of phase III clinical studies of other new drugs
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 In addition, due to the emergence of new treatment options, the course of mHSPC has been greatly extended, and the safety of long-term drug application and the quality of life of patients have also become very important considerations in clinical decision-making
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In clinical application of docetaxel chemotherapy, serious adverse reactions such as neutropenia and febrile neutropenia may occur, which can increase the hospitalization rate of patients, increase the difficulty of clinical management, and greatly reduce the quality of life of patients [ 4,9,10]
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Common adverse reactions of abiraterone are mostly hypertension, hypokalemia, etc.
[5], which are easier to manage; but long-term combination with glucocorticoids may increase the management difficulty of patients with cardiovascular and metabolic complications
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As a new generation of androgen receptor inhibitor, apatamide neither has serious hematological adverse reactions like chemotherapy, nor does it require a combination of hormones, so it is more suitable for long-term use by patients in terms of mechanism
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The ASCO conference announced the long-term follow-up patient quality of life analysis of the TITAN study.
The results showed that patients receiving long-term apatamide + ADT treatment, most patients will not be troubled by or only suffer from a little adverse reaction, and their physical fitness can still be maintained.
Even improved, while still being able to maintain the same quality of life as the baseline, including mood, function, social interaction, etc.
, the patient's pain intensity and pain interference scores remained stable over time, and there was no pain in the TITAN study.
/ The proportion of patients with mild pain and good physical fitness is as high as 80%.
These results further indicate that patients are in good physical condition when they are diagnosed with mHSPC.
Early application of apatamide + ADT treatment at this time can significantly delay the progression of the disease, but also It can enable patients to maintain a high-quality life for a long time
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However, in the current domestic clinical practice, it is common for patients to start treatment with the heavy weapon apatamide when their disease has advanced to an advanced stage, pain or even severe pain.
At this time, the best period for delaying disease progression has been missed, and patients can no longer do so.
Have a high-quality life
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Therefore, for patients with mHSPC, it is very important to use apatamide + ADT for treatment immediately after diagnosis.
On the one hand, it significantly delays the patient's time to mCRPC, and on the other hand, it can enable the patient to maintain a high-quality life for a long time.
It does not affect work or drag down children
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 In summary, the final analysis of the TITAN study confirmed that for patients with mHSPC, early use of apatamide + ADT regimen can significantly prolong OS, provide patients with clear long-term clinical benefits, and at the same time, patients can maintain a long-term high-quality life
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At present, domestic and foreign guidelines also recommend apatamide + ADT as the first-line treatment for mHSPC
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94 Chinese patients were also included in the TITAN study, which once again gave our clinicians confidence in the application of apatamide [1,11]
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It is expected that apatamide, a powerful weapon, can enter medical insurance as soon as possible and benefit more prostate cancer patients
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Expert profile Professor Junqi Wang, Director of Urology, Xuzhou Medical University Affiliated Hospital, Doctor of Medicine, Chief Physician, Jiangsu Province "Six Peaks" Talents, Key Medical Talents Academic Position: Chairman of the Urology Branch of Xuzhou Medical Association Jiangsu Medical Association Urology Deputy Chairman of the Branch, Vice Chairman of the Urological Surgeon Branch of the Jiangsu Medical Association, Deputy Chairman of the Medical Robot Professional Committee of the Jiangsu Medical Association, Member of the Standing Committee of the Urinary Male Reproductive Tumor Committee of the Jiangsu Anti-Cancer Association, Deputy Director of the Quality Control Center for Urology of Jiangsu Province, Chinese Medicine Member of the International Exchange Committee of the Urology Branch of the Association Member of the Urinary and Male Reproductive Oncology Committee of the Chinese Anti-Cancer Association Member of the Renal Cancer Group of the Urinary and Male Reproductive Oncology Committee of the Chinese Anti-Cancer Association Member of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO) References: [1 ] Chi KM, et al.
J Clin Oncol.
2021 PMID:33914595[2] Kim N.
Chi et al.
Lancet Oncol.
2019Nov;20(11):1518-1530[3] Kim N.
Chi et al.
ASCO 2021 .
Abstract 5068.
[4] Sweeney CJ et al.
N Engl J Med.
2015;373:737-46.
[5] Fizazi K, et al.
Lancet Oncol.
.
2019; 20(5):686-700.
[ 6] Chi KN et al.
N Engl J Med.
2019; 381 (1):13-24.
[7] Kyriakopoulos CE et al.
J Clin Oncol.
2018;36(11):1080-1087.
[8] Chi KN et al.
J Clin Oncol.
2019;37(15Suppl):5006.
[9] Patrikidou A, et al.
Clin Oncol.
2017;29(10):e174-e175.
[10] Rulach R, et al.
BJU Int.
2018;121(2):268-274.
[11] The efficacy of apatamide in Chinese patients with mCSPC--subgroup analysis of the TITAN study [A].
CACA-GU 2020.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform