The addition of apalutamide to androgen deprivation therapy (ADT) for a finite duration led to a statistically significant prolongation of prostate-specific antigen (PSA) doubling time and biochemical progression-free survival without impacting testosterone recovery time, results from the phase 3 PRESTO trial showed.
Intermittent and continuous ADT are standard approaches for men with biochemically relapsed, non-metastatic prostate cancer after prostatectomy with a short PSA doubling time and a high risk of developing distant metastases and cancer-related mortality . The phase 3 PRESTO trial (NCT03009981) evaluated the efficacy and safety of intensification of ADT for a finite duration on PSA doubling time suppression enabling longer treatment-free intervals within a framework of intermittent treatment. Dr Rahul Aggarwal (University of California San Francisco, CA, USA) presented the first results .
In the PRESTO trial, 503 patients (prior radical prostatectomy and radiotherapy, PSA doubling-time < 3 months) were randomised 1:1:1 to receive ADT, ADT plus apalutamide (APA), or ADT plus APA plus abiraterone acetate plus prednisone (AAP) for 52 weeks. The primary endpoint was biochemical progression-free survival (PFS). Secondary endpoints included safety, patient-reported quality-of-life (QoL), time to testosterone recovery (> 50 ng/dL) (TTTR), metastasis-free survival (MFS) and time to castration resistance (TTCR).
Median biochemical PFS was improved in ADT + APA versus ADT alone (20.3 vs 24.9 months; HR 0.52; P= 0.00047). Likewise, median biochemical PFS was improved in ADT + APA + AAP versus ADT alone (20.6 vs 26.0 months; HR 0.48; P=0.00008). Biochemical PFS was independent of PSA doubling time (<3 months, 3–9 months). The addition of APA to ADT did not influence TTTR (3.9 months for ADT vs 3.8 months for ADT + APA), whereas the addition of APA + AAP to ADT led to a slight but not statistically significant prolongation of TTTR (4.8 months for ADT + APA + AAP vs 3.9 months for ADT alone). Grade ≥3 adverse events, in particular hypertension, were increased in the ADT + APA + AAP group.
Based on these results, Dr Aggarwal concluded that “the addition of APA to ADT for a finite duration leads to a statistically significant prolongation of biochemical PFS with no impact on testosterone recovery time. Therefore, this treatment regimen could be considered for high-risk patients with a short PSA doubling time. The addition of AAP to ADT + APA does not appear to further benefit the patient.”
- Crook JM, et al. N Engl J Med. 2012;367(10):895–903.
- Aggarwall R, et al. PRESTO: A phase III, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19). Abstract LBA63, ESMO Congress 2022, 09–13 September, Paris, France.
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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma