Prostate Cancer
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The Future of Advanced Prostate Cancer Treatment

Published Online: December 6th 2021 touchREVIEWS in Oncology & Haematology. 2021;17(2):56–7 DOI: https://doi.org/10.17925/OHR.2021.17.2.56
Authors: Axel S Merseburger
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Abstract:
Overview

Professor Axel Merseburger is professor and chairman at the Department of Urology, University of Lübeck, Lübeck, Germany. His key areas of interest are renal cell carcinoma, prostate cancer and transitional cell carcinoma, in particular novel markers and prognostic factors. He is a member of the European Association of Urology guidelines group on renal cell cancer and has served as national and international principal investigator in several phase II/III clinical trials.

Keywords

Advanced prostate cancer, metastatic hormone-sensitive prostate cancer, metastatic castration-resistant prostate cancer, androgen deprivation therapy, prostate-specific membrane antigen (PMSA), positron emission tomography (PET), combination therapy

Article:

Prostate cancer is one of the leading causes of cancer death worldwide.1 However, the emergence of novel hormonal therapies and the increasing availability of sensitive next-generation imaging techniques, such as gallium-88 prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET), has transformed the management of advanced prostate cancer. Numerous agents, including abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T are now approved for advanced prostate cancer.2 Appropriate use of these drugs is essential to optimize outcomes for patients.

In an expert interview, Professor Merseburger discusses the most exciting presentations from the recent European Society for Medical Oncology (ESMO) annual congress and considers their likely impact on clinical practice.

What were the hottest topics and exciting new research from the ESMO congress 2021?

For me, the main focus was on advanced prostate cancer. Data from the STAMPEDE study (NCT00268476) was presented by Gert Attard with high-risk, non-metastatic prostate cancer. A very early intensification in the combination of androgen deprivation therapy (ADT) and abiraterone showed a metastasis-free survival benefit and also an overall survival (OS) benefit. The 6-year survival improved from 77% to 86%, which is clinically meaningful.3

However, since we now have PSMA PET imaging, we will detect more metastatic disease in the future, which needs different treatment. This leads me to the second interesting study, which was the final OS analysis of the ARCHES trial (NCT02677896) presented by Armstrong. This compared ADT with the combination of ADT and enzalutamide in men with metastatic, hormone-sensitive prostate cancer. Results showed a hazard ratio of 0.66 for the combination arm, a significant OS benefit. This trial included 62% of patients with high volume disease, so this was significant metastatic prostate cancer. Of these, 17% had prior docetaxel. The median follow-up was 44 months.These findings give us another treatment option, with abiraterone, apalutamide and now enzalutamide showing a survival benefit in this patient population.

There were multiple discussions about the PEACE-1 (NCT01957436) presentation from Fizazi. Fizazi had shown us a progression-free survival (PFS) benefit at the American Society of Clinical Oncology this year, and now the updated analysis was presented at ESMO. Results showed more than 1 year OS benefit, and PFS was prolonged by 2.5 years for men treated upfront with a triple therapy comprising ADT, docetaxel and abiraterone.5 There are now many discussions around whether the standard treatment in future should be triple therapy or hormone/hormone combinations or docetaxel/hormone combinations. The full paper is not published yet but the data seem very promising. Men that currently receive docetaxel and chemotherapy in combination with ADT should benefit from the triple therapy with abiraterone. However, we have also seen benefits from hormone/hormone combination therapies from the ARCHES and TITAN (NCT02489318) trials,6 and I would personally start with hormone/hormone combination and then sequence treatment.

One last comment is on the phase I COSMIC-021 study (NCT03170960) presented by Agarwal, which investigated the combination of cabozantinib and atezolizumab in patients with metastatic, castration-resistant prostate cancer. This combination demonstrated clinically meaningful activity with a known and manageable safety profile.7 The CONTACT-02 trial (NCT04446117) is a phase III study investigating this combination, and has started worldwide, so we have high hopes of this in future conferences.

How will these key data impact the future of clinical practice?

The key data presented at the ESMO 2021 annual congress have changed the future of prostate cancer treatment. In many countries, men with metastatic prostate cancer only receive ADT. We have known for years that this is not enough, and now we have the PEACE-1 clinical trial data showing a dramatic OS benefit when a triple combination is used. In addition, the ARCHES data have shown an OS benefit with ADT in combination with enzalutamide. We have seen the TITAN data, showing the apalutamide combination with ADT gives an OS benefit in a broad patient population. There is a lot of evidence supporting combined therapies in metastatic prostate cancer. The key message is that ADT alone is not enough in 2021 in metastatic prostate cancer.

Article Information:
Disclosure

Axel S Merseburger has no financial or non-financial relationships or activities to declare in relation to this article.

Compliance With Ethics

This article is an opinion piece and does not report on new clinical data, or any studies with human or animal subjects performed by any of the authors.

Review Process

This is an expert interview and as such has not undergone the journal’s standard peer review process.

Authorship

The named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval for the version to be published.

Correspondence

Axel S Merseburger, Campus Lübeck, University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germany. E: axel.merseburger@uksh.de

Twitter: @amerseburger

Support

Support: No funding was received for the publication of this article.

Access

This article is freely accessible at touchONCOLOGY.com © Touch Medical Media 2021

Acknowledgements

Medical writing support was provided by Katrina Mountfort, freelance medical writer, and funded by Touch Independent Medical Education.

Received

2021-10-21

References

  1. Sung H, Ferlay J, Siegel RL. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.
  2. Swamin U, McFarland TR, Nussenzweig R, et al. Advanced prostate cancer: treatment advances and future directions. Trends in Cancer. 2021;6:702–15.
  3. Attard G, Brown LC, Clarke N, et al. Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): combined analysis from two comparisons in the STAMPEDE platform protocol. Ann Oncol. 2021;32(Suppl.5):S1283–S1346.
  4. Armstrong AJ, Iguchi T, Azad AA, et al. Final overall survival (OS) analysis from ARCHES: a phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC).Ann Oncol. 2021;32(Suppl.5):S1283–S1346.
  5. Fizazi K, Galceran JC, Foulon S, et al. A phase III trial with a 2×2 factorial design in men with de novo metastatic castration-sensitive prostate cancer: overall survival with abiraterone acetate plus prednisone in PEACE-1.Ann Oncol. 2021;32(Suppl.5):S1283–S1346.
  6. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.
  7. Agarwal N, McGregor BA, Maughan BL, et al. Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): results of expanded cohort 6 of the COSMIC-021 study. Ann Oncol.2021;32(Suppl.5):S1283–S1346.

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