Volume 5 - Issue 1, 03 2017

Contemporary Management of Metastatic Hormone-Sensitive Prostate Cancer Back

 

Introduction

At the annual scientific meeting titled “The Changing Landscape of Urological Cancers” organised by the Hong Kong Society of Uro-Oncology (HKSUO) on 7th January 2017, Dr. Darren Ming Chun POON reviewed the latest treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) and shared the results of a retrospective analysis on local patients’ responses to chemohormonal therapy (docetaxel plus androgen deprivation therapy, ADT), which is the first study of such kind in Asia.

Treatment Paradigm for Metastatic Hormone-Sensitive Prostate Cancer

ADT has been the standard treatment for metastatic prostate cancer for several decades.1 However, Dr. Poon noted that some recent studies showed ADT plus chemotherapy could lead to significantly more survival benefits for mHSPC patients compared with ADT alone.

ADT plus chemotherapy is better than ADT alone regarding survival benefits

In the CHAARTED study, which is an open-label, randomised, phase III trial, patients on ADT plus docetaxel had a median overall survival 13.6 months longer than those on ADT alone.1 In addition, in the subgroup with high-volume disease, the median overall survival was 17.0 months longer with combination therapy than with ADT alone.1 Another randomised controlled trial, the STAMPEDE study, revealed that ADT combined with docetaxel could bring about a median overall survival 22 months longer compared with ADT alone among men with metastatic prostate cancer.2 The additional survival benefit of combination therapy was also demonstrated in a meta-analysis, which found that a 9% absolute improvement in survival at four years with ADT plus docetaxel compared to ADT alone among mHSPC patients.3

ADT plus chemotherapy recommended as first-line treatment

Dr. Poon pointed out that, based on the cumulative evidence, some international guidelines, including those from the European Society for Medical Oncology (ESMO), the National Comprehensive Cancer Network (NCCN), and the European Association of Urology (EAU), have recommended ADT plus chemotherapy as first-line treatment for mHSPC patients. 4, 5, 6

Early Experience of the Use of ADT plus Chemotherapy in Hong Kong

Although the efficacy of ADT plus chemotherapy in western population is proven by two pivotal trials, namely CHAARTED and STAMPEDE,1,2 Chinese or Asian data remain limited by far. Dr. Poon shared that, in order to investigate the efficacy and tolerability of the combination therapy in patients of Chinese or Asian origin, the HKSUO conducted a retrospective analysis on mHSPC patients in Hong Kong treated with ADT plus docetaxel.

Local retrospective study conducted – Asia’s first similar research

Clinical data of 32 patients in total from all six public oncology centres locally were analysed (Table 1), with the review period from January 2015 to July 2016. The primary objective is to evaluate the time to the development of castration-resistance, while the secondary one is to find out toxicities related to chemotherapy, prostate-specific antigen (PSA) responses, and the time to PSA nadir.

The patients had a median age of 66 years, with all but one had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. They had a median baseline PSA level of 285.2 ng/mL and the majority of them (96.9%) suffered from a high-volume disease, i.e. presenting four or more bone metastases or visceral metastases. Table 2 shows further characteristics of the patients. The median time from ADT to chemotherapy was 1.5 months. Most of the patients (93.8%) completed six or above cycles of docetaxel. Other treatment details were presented in Table 3.

Location of Oncology Centres

Number of Patients 
(N=32)

Prince of Wales Hospital14
Queen Elizabeth Hospital9
Pamela Youde Nethersole Eastern Hospital4
Queen Mary Hospital2
Tuen Mun Hospital2
Princess Margaret Hospital1

Table 1. Number of patients from different oncology centres.

Patient Characteristics

ADT plus Docetaxel

 (N = 32)

Age – year

 

  Median

66

  Range

53 – 74

ECOG performance status – number (%)

 

0

7 (21.9)

1

24 (75.0)

2

1 (3.1)

Co-morbidities – number (%)

 

  Hypertension

7 (21.9)

  Diabetes mellitus

3 (9.4)

  Ischaemic heart disease

1 (3.1)

Metastasis as initial presentation – number (%)

 

  Yes

31 (96.9)

  No

1 (3.1)*

Symptomatic at presentation (need WHO level II/III analgesics) because of pain – number (%)

9 (28.1)

PSA level at start of ADT – ng/mL

 

  Median

285.2

  Range

44.1 – 5491

PSA level at start of chemotherapy – ng/mL

 

  Median

46.6

  Range

1.2 – 2091

Gleason score – number (%)

 

  < 8

4 (12.5)

  8 – 10

25 (83.3)

  Unknown

3 (9.4)

Baseline haemoglobin – g/dL

 

  Median

13.0

  Range

9.6 – 14.4

Baseline alkaline phosphatase – U/L

 

  Median

207

  Range

64 – 2949

Disease location – number (%)

 

  Bone only

24 (75.0)

  Lymph node

7 (21.9)

  Lung

1 (3.1)

  Liver

0

Number of bone metastases – number (%)

 

  0

2 (6.3)#

  < 4

1 (3.1)§

  4 – 10

12 (37.5)

  > 10

14 (43.8)

Superscan

3 (9.4)

Table 2. Baseline characteristics of the patients.

* The patient was previously treated with radical prostatectomy and refused to undergo salvage radiotherapy during progression with metastatic disease.

# The patients had metastases at lung or lymph node.

§The patient had large sacral metastases.

WHO = World Health Organisation

Treatment Details

ADT plus Docetaxel

(N = 32)

Time from ADT to chemotherapy – months

 

  Median

1.5

  Range

0.03 – 6.23

Chemotherapy dose – number (%)

 

75 mg/m2

31 (96.9)

60 mg/m2

1 (3.1)

Chemotherapy cycles – number (%)

 

< 6

2 (6.3)

6

27 (84.4)

7-10

3 (9.4)

Reasons for chemotherapy discontinuation – number (%)

 

Completed 6 or above cycles

30 (93.8)

Toxicity

1 (3.1)

Disease progression

1 (3.1)

Granulocyte colony stimulating factor – number (%)

 

Primary indication

5 (15.6)

Secondary indication

6 (18.8)

Table 3. Details of the treatment received by the patients.

After a median follow-up of 11.4 months, the median time to castration-resistance was 19.5 months (Figure 1), which is comparable to the result found in the CHAARTED study (i.e. 20.2 months).1 In addition, the median time to PSA nadir was 7 months and all patients achieved a PSA response, i.e. over 50% drop from the baseline level. Regarding chemotherapy-related side effects on grade 3 or 4, the rates of neutropenia, febrile neutropenia and anaemia were 40.6%, 12.5% and 3.1%, respectively (Table 4).

Figure 1. Time to the development of castration-resistance.

Figure 1. Time to the development of castration-resistance.

Treatment-related side effects

Grade 1 or 2 – number (%)

(N=32)

Grade 3 or 4 – number (%)

(N=32)

Febrile neutropenia

0

4 (12.5)

Neutropenia

3 (9.4)

13 (40.6)

Thrombocytopenia

0

0

Anaemia

19 (59.4)

1 (3.1)

Neuropathy

13 (25.0)

0

Fatigue

14 (43.8)

0

Diarrhoea

5 (15.6)

0

Stomatitis

5 (15.6)

0

Table 4. Treatment-related side effects encountered by the patients.

Efficacy of ADT plus chemotherapy is comparable among Chinese/Asian and western patients

Dr. Poon noted that, in view of the study results, compared with their western counterparts, Chinese or Asian mHSPC patients are expected to have a similar efficacy of ADT plus chemotherapy at an early stage, with favourable biochemical responses. However, their risk of having treatment-related haematological toxicities is deemed higher, so it is important to select patients cautiously and consider the use of granulocyte colony stimulating factor (GCSF) before starting the combination therapy. Dr. Poon said that the overall survival and other clinical outcomes would be followed up in the future.

Questions & Answers

Q1: What is the age considered proper for elderly patients to receive ADT plus chemotherapy?

Dr. Poon: The local retrospective study only focused on a group of relatively young patients treated with the combination therapy at an early phase. But according to some local physicians’ clinical experience, the combination therapy had been given to elderly patients aged up to 80 years. However, I think that age is not the only factor in deciding whether to initiate the combination therapy. Other features, such as general health conditions and presence of co-morbidities, should be also considered to select patients fit for ADT plus chemotherapy.

Q2: Did the patients included in the local study receive prednisone?

Dr. Poon: In our cohort, the patients did not receive prednisone or any other steroid with chemotherapy, just like the setting in the CHAARTED study.1 On the other hand, for patients with metastatic castration-resistant prostate cancer, local doctors usually prescribe prednisone with chemotherapy, which seems quite tolerable to the patients in terms of side effects. However, for those with diabetes or co-existing infections, caution is warranted regarding the treatment.

Take-Home Messages

  • There is evidence suggesting that ADT plus chemotherapy can provide significantly better survival benefits for mHSPC patients compared with ADT alone.
  • Some major professional bodies have recommended ADT plus chemotherapy as first-line treatment for mHSPC patients.
  • As per a Hong Kong retrospective study, ADT plus chemotherapy leads to a similar efficacy in terms of the time to castration-resistance among Chinese or Asian mHSPC patients compared to their western counterparts.
  • Due to the possibly higher rate of chemotherapy-related haematological toxicities among Chinese or Asian patients, prudent patient selection and consideration of using GCSF is warranted before initiating the combination therapy.

 

References

  1. Sweeney CJ, et al. N Engl J Med. 2015;373:737-46.
  2.  James ND, et al. Lancet. 2016;387:1163-77.
  3. Vale CL, et al. Lancet Oncol. 2016;17:243-56.
  4. Parker C, et al. Ann Oncol. 2015;Suppl 5:v69-77.
  5. Carroll PR, et al. J Natl Compr Canc Netw. 2016;14:509-19.
  6. Cornford P, et al. Eur Urol. 2016 Aug 31. pii: S0302-2838(16)30469-9. [Epub ahead of print]