NICE backs Janssen’s Erleada®▼ (apalutamide) for Hormone-Sensitive Metastatic and Hormone-Relapsed Non-Metastatic Prostate Cancer

NICE backs Janssen’s Erleada^®▼ (apalutamide) for Hormone-Sensitive Metastatic and Hormone-Relapsed Non-Metastatic Prostate Cancer

• Apalutamide has been shown to increase the time until the disease progresses and how long patients live, according to data from the Phase III TITAN and SPARTAN studies^1,2 [i]^,[ii]
• Eligible prostate cancer patients will now have access to apalutamide via the National Health Service (NHS) in England and Wales^3,4 [iii]^,[iv]

High Wycombe, 8^th September 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the National Institute of Health and Care Excellence (NICE) has reconsidered its previous decision for Erleada^®▼ (apalutamide), and today published two positive Final Appraisal Determinations (FADs) recommending the use of apalutamide in combination with androgen deprivation therapy (ADT) to treat prostate cancer.^3,4 Apalutamide plus ADT is recommended for two indications within its marketing authorisation:

• As an option for treating hormone-sensitive metastatic prostate cancer (mHSPC) in adults, only if docetaxel is not suitable or cannot be tolerated³
• As an option for treating hormone-relapsed non-metastatic prostate cancer (nmHRPC)* that is at high risk** of metastasising in adults.⁴

The decision means eligible prostate cancer patients with mHSPC and nmHRPC will now have access to apalutamide via the National Health Service (NHS) in England and Wales.

There are over 42,500 people diagnosed with prostate cancer each year in England and Wales.⁵[v] It is estimated that 13 percent have metastatic disease at diagnosis, and those with mHSPC also tend to have a poor prognosis, with a median overall survival (OS) of approximately 45 months in three large randomised controlled trials when starting standard androgen deprivation therapy (ADT).7^,6 [vi]However, there are some patients who cannot tolerate or are unsuitable for docetaxel plus ADT.3 NICE concluded that identifying people for whom docetaxel was contraindicated or unsuitable would be based on a clinical framework considering individual patient risk.³ Now apalutamide plus ADT has been recommended for use when docetaxel is unsuitable or cannot be tolerated, these patients can now access an alternative treatment option that is generally better tolerated than docetaxel plus ADT and is likely to be more effective than ADT alone.³

Approximately 87 percent of those with prostate cancer suffer from the non-metastatic form of the disease at diagnosis – meaning that the cancer has not spread to other parts of the body.⁷[vii] If the disease is hormone-relapsed (also known as castration-resistant), it no longer responds to medical or surgical treatments that lower testosterone.⁸[viii]  Around 90 percent of patients with hormone-relapsed prostate cancer will eventually develop bone metastases, which can be a key cause of complications and death.⁸ Extending the period without metastases is therefore an important treatment goal.

“Despite significant advances in treatment options through research in advanced prostate cancer management, unfortunately in some patients the prognosis can be poor,” said Professor Amit Bahl***, Consultant Clinical Oncologist and Uro-oncology Research Lead at Bristol Haematology & Oncology Centre. “The addition of apalutamide to the treatment pathway provides eligible prostate cancer patients with a therapy option with significant survival benefit as shown in clinical trials. It is a vital step towards improving outcomes in prostate cancer and enabling patients to have a better prognosis.”

NICE’s decision for mHSPC is based on data from the phase III TITAN study, which concluded that apalutamide plus ADT is clinically effective compared with placebo plus ADT.³ NICE also concluded that the data showed that median radiographic progression-free survival for people randomised to apalutamide plus ADT was not reached and for people randomised to placebo plus ADT, it was 22.1 months (hazard ratio 0.5, 95% CI 0.4 to 0.6).³

Published data from TITAN confirmed that the safety profiles for apalutamide plus ADT, versus placebo plus ADT, were similar with 42 percent versus 41 percent of Grade 3/4 AEs observed respectively.¹ The most common Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).¹ Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.¹ Overall, the NICE committee concluded that adverse effects with apalutamide plus ADT are tolerable.³

In addition, NICE’s decision around the nmHRPC indication is based on the results of the phase III SPARTAN trial.⁴ In the trial median metastases-free survival for people randomised to apalutamide plus ADT was 40.5 months and for people randomised to placebo plus ADT it was 15.7 months (hazard ratio 0.30, 95% confidence interval [CI] 0.24 to 0.36). Furthermore, median overall survival (OS) for people given apalutamide plus ADT was 73.9 months, compared to 59.9 months in the placebo group.⁴ Apalutamide plus ADT also improved median time to second progression (progression on next treatment), 55.6 months, compared to the control group (41.2 months).⁴ Finally, mean change in EQ-5D-3L visual analogue score showed improvements in the apalutamide plus ADT arm compared with the placebo plus ADT arm at cycles 21 (mean difference 3.03) and 25 (mean difference 3.28), p<0.05.⁴

The most common Grade 3/4 treatment-emergent adverse events (AEs) in the SPARTAN study were hypertension (14.3 percent vs. 11.8 percent), rash (5.2 percent vs. 0.3 percent), fall (1.7 percent vs. 0.8 percent) and fracture (2.7 percent vs. 0.8 percent).² Treatment discontinuation due to adverse events was 10.6 percent in the apalutamide arm compared to 7 percent in the placebo arm.² Rates of serious adverse events were similar in the apalutamide in combination with ADT arm versus placebo in combination with ADT arm (24.8 percent vs. 23.1 percent respectively).² Overall, the NICE committee concluded that adverse effects with apalutamide plus ADT are tolerable.⁴

“Today’s positive recommendation for apalutamide marks a significant milestone in our mission to bring new therapeutic options to patients with mHSPC and nmHRPC,” said Sarah Scanlon, Business Unit Director, Oncology, Haematology and Pulmonary Hypertension. “We are delighted that NICE has given the green light for apalutamide for both indications and look forward to seeing these groups of patients benefit from a new treatment option.”

*Hormone-relapsed non-metastatic prostate cancer (nmHRPC) can also be referred to as castration-resistant non-metastatic prostate cancer (nmCRPC).

**High risk is defined as a blood prostate specific antigen (PSA) level that has doubled in 10 months or less on continuous ADT.⁴

*** Professor Amit Bahl has not received consultancy honoraria from Janssen. He has not been compensated for any media work.

1 Chi, Kim N., et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. The New England Journal of Medicine, vol. 381, no. 1, 2019, pp. 13–24.

² Smith, Matthew R., et al. Apalutamide Treatment and Metastasis-Free Survival in Prostate Cancer. The New England Journal of Medicine, vol. 378, no. 15, 2018, pp. 1408–1418.

³ National Institute for Health and Care Excellence. Final appraisal document. Apalutamide with androgen deprivation therapy for treating hormone-sensitive metastatic prostate cancer. Available at: https://www.nice.org.uk/guidance/gid-ta10423/documents/. Last accessed September 2021.

⁴ National Institute for Health and Care Excellence. Final appraisal document. Apalutamide with androgen deprivation therapy for treating high-risk hormone-relapsed non-metastatic prostate cancer. Available at: https://www.nice.org.uk/guidance/gid-ta10423/documents/. Last accessed September 2021.

5 Prostate Cancer UK. About Prostate Cancer. Available at: https://prostatecanceruk.org/prostate-information/about-prostate-cancer. Last accessed September 2021.

6 European Association of Urology. Updated guidelines for metastatic hormone-sensitive prostate cancer: abiraterone acetate combined with castration is another standard. Available at: https://uroweb.org/wp-content/uploads/Mottet-N.-et-al.-Eur-Urol-733316-321.-Updated-Guidelines-for-Metastatic-Hormone-sensitive-PCa-Abiraterone-Acetate.pdf. Last accessed September 2021.

7 National Prostate Cancer Audit. Annual Report 2020: Results of the NPCA Prospective Audit in England and Wales for men diagnosed from 1 April 2018 to 31 March 2019. January 2021. Available at: https://www.npca.org.uk/content/uploads/2021/01/NPCA-Annual-Report-2020_Final_140121.pdf. Last accessed September 2021.

8 Saad. F. Guidelines for the management of castrate-resistant prostate cancer. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997826/ Last accessed September 2021.