PROpel Phase III trial positive results of LYNPARZA® (olaparib) plus abiraterone in 1st-line metastatic castration-resistant prostate cancer published in New England Journal of Medicine Evidence

Combination reduced risk of disease progression by 34% vs. standard-of-care in patients irrespective of homologous recombination repair gene mutation status

Reno, Nevada (UroToday.com) -- Results from the PROpel Phase III trial showed that LYNPARZA® (olaparib), jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada, in combination with abiraterone significantly improved radiographic progression-free survival (rPFS) versus abiraterone alone as a 1st-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations. The results, showing the combination reduced the risk of disease progression or death by 34% versus abiraterone alone (based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001), are now published in the New England Journal of Medicine (NEJM) Evidence.1


Prostate cancer is the second most common cancer in male patients, causing approximately 375,000 deaths in 2020.1 In clinical trial settings, overall survival for patients with mCRPC is approximately 3 years, while in the real-world setting this is shorter.2-5 Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.6-10 HRR gene mutations occur in approximately 20-30% of patients with mCRPC.3,11

Noel Clarke, Urological Surgeon and Professor of Urological Oncology at The Christie/Salford Royal Hospitals and University of Manchester; the PROpel trial joint Chief investigator and joint lead author of the NEJM Evidence manuscript, said: “It is critically important that we identify new first-line treatment options for patients with metastatic castration-resistant prostate cancer. The data published in NEJM Evidence emphasize the therapeutic potential of combining olaparib with abiraterone and prednisone and demonstrate efficacy in a wider group of patients beyond those with documented DNA repair deficiency.”

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “These data demonstrate that the combination of LYNPARZA with abiraterone and prednisone afforded patients a median radiographic progression-free survival of over two years, regardless of biomarker status. If approved, the combination will offer patients with and without HRR gene mutations a much needed new treatment option.”

Dr. Eliav Barr, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, said: “Publication of the PROpel data in NEJM Evidence reflects the benefit seen with the combination of LYNPARZA plus abiraterone and prednisone in the first-line setting of metastatic castration-resistant prostate cancer, and we are pleased that these data have been selected for one of the first issues of this new journal."
In September 2021, at a planned interim analysis, the Independent Data Monitoring Committee concluded that the PROpel trial met the primary endpoint of rPFS. The results were presented in February 2022 during 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and additional data on Safety and Tolerability as well as Pharmacokinetics were presented at ASCO 2022 on June 6, 2022.

In the PROpel Phase III trial, on the primary endpoint, LYNPARZA in combination with abiraterone improved median rPFS to 24.8 months versus 16.6 for abiraterone alone. Results also showed that LYNPARZA in combination with abiraterone extended median rPFS by BICR (blinded independent central review) analysis by almost a year, with a median rPFS of 27.6 months versus 16.4 with abiraterone alone. Results also showed a favorable trend towards improved overall survival (OS) with LYNPARZA plus abiraterone versus abiraterone alone, however, the difference did not reach statistical significance at the time of this data cut-off (28.6% maturity; based on a HR of 0.86; 95% CI 0.66-1.12; P=0.29). Data from the additional secondary efficacy endpoints of time to first subsequent therapy (TFST) (HR, 0.74; 95% CI, 0.61-0.90) and second progression-free survival (PFS2) (HR, 0.69; 95% CI, 0.51-0.94); and exploratory endpoints including objective response rate (ORR) (odds ratio, 1.60; 95% CI,1.02-2.53) as well as prostate-specific antigen levels, determining time to PSA progression (HR, 0.55; 95% CI, 0.45-0.68), further support the treatment benefit of LYNPARZA and abiraterone compared to abiraterone alone in the overall trial population.

The safety and tolerability of LYNPARZA in combination with abiraterone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. There was no increase in the rate of discontinuation of abiraterone in patients treated with LYNPARZA in combination with abiraterone, and no detrimental effect on health-related quality of life versus those treated with abiraterone alone (FACT-P (Functional Assessment of Cancer Therapy-Prostate) questionnaire).

LYNPARZA is approved in the US for patients with HRR gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent (NHA).

References:

  1. AstraZeneca. Lynparza plus abiraterone reduced risk of disease progression by 34% vs. standard-of-care in 1st-line metastatic castration-resistant prostate cancer. Available at https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/lynparza-combo-delays-progression-risk-in-prostate-cancer.html. Accessed May 2022.
  2. Ng K, et al. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting. Oncol Ther. 2020;8:209–230.
  3. Shore N, et al. Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors. Adv Ther. 2021;38:4520–4540.
  4. Wallis C, et al. Real-World Use of Androgen-Deprivation Therapy: Intensification Among Older Canadian Men With de Novo Metastatic Prostate Cancer. JNCI Cancer Spectrum. 2021;5(6):pkab082.
  5. George D, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clinical Genitourinary Cancer. 2020 Aug;18(4):284-294.
  6. Kirby, M, et al. Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice, 2021;65(11):1180-1192.
  7. Smith MR, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918-25.
  8. UroToday. What is Changing in Advanced Prostate Cancer? Available at https://www.urotoday.com/journal/everyday-urology-oncology-insights/articles/122176-what-is-changing-in-advanced-prostate-cancer.html. Accessed May 2022.
  9. Liu J, et al. Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database. Scientific Report. 2020;10(4240):2020.
  10. George DJ, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clin Genitourin Cancer. 2020; 18:284-294.
  11. Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015; 373:1697-1708.

Source: Evidence, PROpel. 2022. "Propel Phase III Trial Positive Results Of LYNPARZA® (Olaparib) Plus Abiraterone In 1St-Line Metastatic Castration-Resistant Prostate Cancer Published In New England Journal Of Medicine Evidence". Astrazeneca-Us.Com.  

Related Content:

Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer
email news signup