Evolution of Prostate Cancer Treatment Gathers Speed

A 2019 study for the World Journal of Oncology¹ puts prostate cancer (PC) as the second most common cancer diagnosis amongst men globally, and one of the leading causes of cancer deaths. The more positive news, according to data from the US National Cancer Institute,² is that the 5-year survival rate for all PC (in the US) is 98% – but the same study shows that this rate drops to just 31% in the case of late-stage diagnosis. 

So, what are the current treatment options for this too-prevalent disease – and the outlook for the future as clinical outcomes evolve?

The evolution of treatment

Prostate cancer has defined clinical states relating to the tumor’s response to hormone therapy and the presence of metastases. These four broad segments, listed below, allow doctors to classify patients and determine how best to treat and manage them: 

• Hormone-sensitive without metastases (M0 HSPC)

• Hormone-sensitive with metastases (M1 HSPC)

• Castration-resistant without metastases (M0 CRPC)

• Castration-resistant with metastases (M1 CRPC)

Typically, the mainstay of systemic PC treatment is hormonal androgen deprivation therapy (ADT). However, if the patient becomes resistant to hormone therapy and the disease progresses then additional drug classes can offer survival benefit. 

In recent years, we’ve seen a hive of pharmaceutical activity in prostate cancer treatment and these advances have entirely changed the treatment algorithm for this setting. Less than a decade ago, docetaxel was the traditional standard of care for patients with metastatic castration-resistant PC – then the next generation of androgen signalling inhibitors (abiraterone acetate and enzalutamide) entered the market. Further treatment options for this patient group include an additional chemotherapy (cabazitaxel), an immunotherapeutic agent (sipuleucel-T) and an alpha-emitting bone-seeking radioisotope. May 2017 also saw the FDA approve the first anti-PD-1 immunotherapy (pembrolizumab) for PC patients whose cancer displays specific characteristics. 

More recently, research and development within the PC treatment field has expanded the focus of second-generation hormonals towards non-metastatic castration-resistant PC and metastatic hormone-sensitive cancers. Following approval extensions for the established products, successive hormonal agents (apalutamide and darolutamide) arrived to treat non-metastatic castration-resistant PC and were approved by the FDA in Feb 2018 and July 2019, respectively. 

The future – the doctors’ perspective

From a research perspective (and indeed Ipsos’ marketing research perspective), prostate cancer is one of the most interesting, yet challenging, solid tumours to focus on – particularly in view of the new treatment options on the horizon. 

In 2019, Ipsos conducted research among PC-treating doctors to understand which of the options in development was generating the most anticipation. Specifically, we conducted online quantitative research to capture doctors’ reactions to clinical trial data presented for high-incidence cancer types at ASCO, the world’s largest global oncology conference and where the most practice-changing developments in cancer treatment are typically revealed. Our research, conducted the week after ASCO 2019 with attending US doctors, sought to identify which PC clinical trials our respondents perceived to be the most interesting. Results were as follows:

• ENZAMET (Xtandi, enzalutamide) was the trial most likely to be spontaneously mentioned by the doctors we surveyed, both for the greatest impact on clinical practice (35%) and specifically on prostate cancer patients (39%).

• TITAN (Erleada, apalutamide) was mentioned by 19% of surveyed doctors for both metrics. 

Both trials sought to extend products currently approved for metastatic castration-resistant PC into metastatic hormone-sensitive PC – and the trial data for both enzalutamide³ and apalutamide⁴ showed a significant benefit to patients in the latter group. 

What could this mean for PC treatment?

Apalutamide went on to receive FDA approval for metastatic hormone-sensitive PC in September 2019, with enzalutamide following closely behind in December. We wait eagerly to see whether and how these approvals will change the PC treatment landscape. However, we also raise the question of whether doctors are already looking to the next developments in this segment. In other words, how long do pharma companies have to embed these agents into the market with new pipeline developments already in view? Just one example is the ARASENS⁵ trial comparing 1^st line ADT + docetaxel against ADT + docetaxel + darolutamide. In addition, new drug classes such as the PARP inhibitors have shown strong clinical trial data and may join the treatment portfolio for metastatic castration-resistant PC.

As trial data are released and guidelines updated, the standard of care in each clinical state can evolve, along with the sequencing of treatments. Enzalutamide has now garnered approval across three of the four states of prostate cancer, which could raise questions around the optimal treatment sequencing of patients. For example, what is the overall survival benefit of enzalutamide if used in metastatic hormone-sensitive PC instead of metastatic castration-resistant PC? Does treating with enzalutamide in the earlier hormone-sensitive PC setting extend survival, or should enzalutamide be reserved for castration-resistant PC? Is re-challenge with the same agent (or class) effective after progression to a later segment of PC? A key consideration when launching into this market may well be around doctors’ perceptions of how to use the agents effectively and in which sequence.

All of these questions and more will be answered in time, but from our standpoint it is apparent that the evolution of prostate cancer treatment is gathering speed, offering new hopes for patients affected by this high-incidence disease.

Amy Butcher is Director, Global Oncology Monitor, Ipsos.

About the research

Ipsos conducted an online quantitative research survey among doctors treating prostate cancer in the US. All respondents had attended ASCO 2019 and all had personally initiated drug therapy for the treatment of their prostate cancer patients. The market research, conducted via an online doctor panel, was carried out between June 5^th–10^th 2019. In total, 75 treaters of prostate cancer were surveyed, with a split of 46 oncologists and 29 urologists. Data are © Ipsos 2020.

Notes

1. www.ncbi.nlm.nih.gov/pmc/articles/PMC6497009/

2. seer.cancer.gov/statfacts/html/prost.html

3. www.nejm.org/doi/10.1056/NEJMoa1903835

4. www.nejm.org/doi/10.1056/NEJMoa1903835

5. ascopubs.org/doi/abs/10.1200/JCO.2018.36.6_suppl.TPS383