apalutamide / Generic mfg. - LARVOL DELTA

Overall survival from PANTHER: A multicenter trial of apalutamide, abiraterone acetate plus prednisone in Black and White patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2024) - P2 | "Key baseline prognostic factors for the Black and White cohorts, respectively included: Gleason score 8-10 (56%; 56%), KPS 70-80% (26%; 18%), median age (67; 72), median PSA 15.20; 17.56), median time from diagnosis to enrollment (4.6 years; 3.3 years), visceral metastases (23.7%; 18.0%), prior docetaxel (33%; 44%). We hypothesize that treatment with the combination of A+AAP may result in clinical efficacy in Black men with mCRPC. Further prospectively powered studies of dual androgen receptor pathway inhibition with AAP among Black men with advanced prostate cancer are needed to determine the potential clinical benefits in this understudied population."

Clinical • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Randomized Three-Arm Trial to Evaluate the Effect of Neoadjuvant Apalutamide Alone or in Combination with Abiraterone Acetate and GnRH Agonist on Enhancing Surgical Outcome of Nerve-Sparing Radical Prostatectomy in Men with High-Risk Prostate Can (AUA 2025) - P2 | "We report the outcomes of a prospective randomized trial evaluating the effect of neoadjuvant Apalutamide (Apa) +/- abiraterone acetate/prednisone (AAP) and a gonadotropin-releasing hormone (GnRH) agonist on nerve sparing during RP in men with high-risk PCa. Early analysis of the study suggest that neoadjuvant apalutamide prior to surgery resulted in faster continence recovery without compromising surgical outcomes or safety for patients with High risk PCa undergoing nerve sparing RP. Final analysis will be conducted in June 2025."

Clinical • Combination therapy • Prostate Cancer

Prognostic significance of PSA>0.2 after 6-12 months treatment for metastatic hormone-sensitive prostate cancer (mHSPC) intensified by androgen-receptor pathway inhibitors (ARPI): A multinational real-world analysis of the IRONMAN registry. (ASCO 2025) - "Intensification agents were: abiraterone acetate (576, 44.7%), apalutamide (283, 22.0%), darolutamide (135, 10.5%), or enzalutamide (294, 22.8%), and 122 (8.7%) received docetaxel in addition to ADT-ARPI. IRONMAN provides large real-world data validating the poor prognosis of mHSPC with PSA>0.2 after 6-12 months ADT-ARPI treatment and these patients could be targeted for intensification in future trials. Conversely, PSA<0.02 at 6-12 months defines the best prognosis and may be of interest for de-intensification strategies. OS and PFS outcomes by 12-month PSA strata."

Clinical • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Final results from PRESTO: A phase III open-label study of combined androgen blockade in patients (pts) with high-risk biochemically relapsed prostate cancer (BRPC) (AFT-19) (ESMO 2025) - P3 | "Background Prior analyses of PRESTO demonstrated that apalutamide (APA) prolonged PSA progression-free survival (PSA-PFS) without negatively impacting quality of life (QOL) in pts with high-risk BRPC...Pts were randomized 1:1:1 to receive a finite 52-week treatment course with androgen deprivation therapy (ADT), ADT + APA, or ADT + APA + abiraterone acetate with prednisone (AAP)...The difference in RMST over the first 48 months for MFS between ADT + APA vs ADT was 2.92 months (95% CI: 0.45 – 5.39) and for ADT + APA + AAP vs ADT was 2.41 months (95% CI: -0.20 – 4.62). Table: LBA88 Endpoint Comparison Hazard Ratio 95% CI Metastasis-free survival ADT + APA vs ADT 0.80 0.56 – 1.13 ADT + APA + AAP vs ADT 0.92 0.66 – 1.28 Time to castration resistance ADT + APA vs ADT 0.58 0.36 – 0.95 ADT + APA + AAP vs ADT 0.55 0.34 – 0.90 Time to subsequent treatment ADT + APA vs ADT 0.75 0.56 – 1.00 ADT + APA + AAP vs ADT 0.64 0.47 – 0.86 PSA-PFS in the testosterone-recovered subset..."

Clinical • Late-breaking abstract • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer

Evaluation of circulating tumor DNA-based genomic alterations in patients with mCSPC treated with Apalutamide: CUARTET study in Japan (ESMO Asia 2025) - P4 | "CUARTET study highlighted consistent efficacy and safety of Apa in Japanese patients with mCSPC. The presence of baseline ctDNA was associated with shorter time to CRPC and OS. Some GAs may cause early progression on treatment with AR pathway inhibitors that need to be further clarified in future studies."

Circulating tumor DNA • Clinical • Castration-Resistant Prostate Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer

Association of race and survival in patients treated with apalutamide: Pooled analysis of two phase 3 trials. (PubMed, Cancer) - "In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS."

Journal • P3 data • Retrospective data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Pooled Analysis of the SOLAR and SATURN Clinical Trials Comparing Progression of Synchronous Versus Metachronous Prostate-specific Membrane Antigen-defined Oligometastatic Prostate Cancer Following Systemic and Tumor-directed Therapy. (PubMed, Eur Urol Oncol) - P2 | "All patients received 6 mo of intensified systemic therapy (leuprolide, abiraterone acetate with prednisone, and apalutamide) and stereotactic body radiotherapy to oligometastases. Among 50 patients (24 synchronous and 26 metachronous), the synchronous omCSPC group had a significantly higher PSA response rate (83% vs 50%; p = 0.018) and significantly longer PFS and eugonadal PFS (p < 0.05). The metachronous subgroup with prior ADT had worse outcomes, suggesting increasing resistance with repeated systemic therapy."

Journal • Retrospective data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Statin Use in Patients With Advanced Prostate Cancer in the TITAN and SPARTAN Trials. (PubMed, JAMA Netw Open) - "In this cohort study, statin exposure was associated with longer OS in patients treated with apalutamide. Statin-exposed patients had a higher risk of grade 3 or greater cardiac AEs, which may reflect their preexisting cardiovascular comorbidity."

Clinical • Journal • Cardiovascular • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Early Results from a Randomized Phase II Trial Testing Apalutamide and Stereotactic Body Radiation Therapy for Low-Burden Mhspc (NCT05717660) (ASTRO 2025) - P2 | "Despite the early phase of the trial, a non significant trend in favour of SBRT addition was found, with a 21% odds increase in the overall sample. Patients with lower burden of disease (< 3 distant metastases) may gain significant advantage from concomitant treatment. PERSIAN trial completed the accrual in November 2024, early results about complete biochemical response at 6 months in the complete cohort will be available in the second half of 2025."

Clinical • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

FORMULA-509: A Multicenter Randomized Trial of Postprostatectomy Salvage Radiotherapy and 6 months of a GNRH Agonist with Either Bicalutamide or Abiraterone Acetate plus Prednisone and Apalutamide. (PubMed, Eur Urol) - P2 | "This study did not reveal a benefit for the overall population, but addition of AAP + apalutamide (vs bicalutamide) to sRT and ADT improved PFS and MFS in the prespecified subgroup with PSA >0.5 ng/ml."

Journal • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Prostate Cancer • Solid Tumor

Intensified hormonal blockade with SBRT in PSMA-PET detected oligometastatic prostate adenocarcinoma: Results from the phase II Metacure trial cohorts B2 and the B2 expansion. (ASCO 2025) - P2 | "Cohort B2 randomized pts to metastasis-directed SBRT with either 10 months of ADT + apalutamide + abiraterone acetate plus prednisone (ADT+APA+AAP) or ADT + apalutamide (ADT+APA). SBRT with short course intensified hormonal blockade was well tolerated and led to durable disease control in pts with PSMA PET-detected metachronous oligometastatic prostate cancer."

Metastases • P2 data • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer

TRIPLE-SWITCH (SWOG/CCTG-PR26): A randomized phase III clinical trial for the addition of docetaxel to androgen receptor pathway inhibitors in patients with metastatic castration sensitive prostate cancer (mCSPC) and suboptimal PSA response (NCT06592924). (ASCO 2025) - P3 | "Arm 1 will continue standard ADT + ARPI (abiraterone acetate with prednisone, apalutamide, enzalutamide or darolutamide). Correlative studies will explore the prognostic and predictive value of circulating tumor DNA (ctDNA) and the association between molecular signatures in primary prostate cancer tissue and clinical outcomes. Enrolment has been initiated in January 2025 and is ongoing."

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Double-Blinded Placebo-Controlled Biomarker Stratified Randomized Trial of Apalutamide (APA) and Radiotherapy for Recurrent Prostate Cancer (NRG GU006, BALANCE trial) (ASTRO 2025) - "Patients with transcriptionally defined luminal B tumors derived improvement in clinically meaningful endpoints from the addition of APA to SRT. PAM50 represents the first prospectively validated predictive biomarker for hormone therapy in prostate cancer in a randomized trial."

Biomarker • Clinical • Late-breaking abstract • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Local Therapy and Outcome in De Novo Metastatic Prostate Cancer: Individual Patient Data Analysis of the TITAN and ARASENS Trials (ASTRO 2025) - "Materials/ In the ARASENS trial, patients with mPCa were randomly assigned to ADT plus docetaxel versus ADT plus docetaxel plus darolutamide. in the TITAN trial, patients were randomly assigned to ADT (+/-docetaxel) versus ADT plus apalutamide... In this IPD analysis of two trials, exposure to local therapy in de novo mPCa was associated with evidence of superior OS in patients treated with either ADT or ADT plus ARPI, respectively. The findings emphasize the role of prostate directed local therapy even in ARPI treated men with de novo mPCa."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A RARE CASE OF PROSTATE ADENOCARCINOMA WITH RAPID TRANSFORMATION INTO METASTATIC SMALL CELL PROSTATE CANCER (WRMC 2026) - "Empiric treatment was initiated with apalutamide, an ARPI, and leuprolide, a GnRH agonist...The patient completed Transarterial Chemobolization (TACE) and subsequently started carboplatin, etoposide, and durvalumab 14 months after the diagnosis...A literature review showed 2 retrospective phase 2 studies w/ durvalumab or atezolizumab + chemotherapy. SCPC has little prospective data to guide clinical decision making, and we hope this case helps to shed light on this."

Clinical • Metastases • Endocrine Disorders • Genito-urinary Cancer • Hepatology • Metabolic Disorders • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Radiographic Progression Without Corresponding Prostate-specific Antigen Progression in Patients with Metastatic Castration-sensitive Prostate Cancer Receiving Apalutamide: Secondary Analysis of the TITAN Trial. (PubMed, Eur Urol Oncol) - "This study found that nearly half of the patients with mCSPC treated with apalutamide who experienced radiographic progression developed it without corresponding PSA progression, suggesting that heavy reliance on PSA monitoring may be inadequate for assessing disease activity in this context."

Journal • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A multicenter, single-arm, phase II trial of androgen deprivation therapy in combination with apalutamide in patients with high risk of recurrence after radical prostatectomy (ARES study) (ESMO Asia 2025) - P2 | "Adjuvant apalutamide (240 mg/day) plus ADT demonstrated promising efficacy (100% 6-month bPFS) and manageable safety in high-risk LPC patients post-RP. These interim results support further investigation of this regimen as a potential strategy to reduce recurrence in this population."

Clinical • Combination therapy • P2 data • Oncology • Prostate Cancer

Transdermal oestradiol (tE2) patches as androgen deprivation therapy (ADT): Efficacy and safety of combining with androgen receptor pathway inhibitors (ARPIs) in metastatic (M1) prostate cancer—Randomised comparison from the STAMPEDE trial platform. (ASCO-GU 2025) - P2/3 | "However, there is currently no data on the use of androgen receptor pathway inhibitors (ARPIs) (abiraterone, enzalutamide or apalutamide) with tE2. PSA responses were similar in pts treated with tE2+ARPI or LHRHa+ARPI further supporting the use of tE2 patches for ADT in prostate cancer management. tE2 patches provide patients with ADT choices about expected toxicity profiles, including reduced hot flushes (and subsequent impact on quality of life), and mode of administration."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CMS Announces Selection of Drugs for Third Cycle of Medicare Drug Price Negotiation Program, Including First-Ever Part B Drugs (CMS Press Release) - "Erleada; Kisqali; Lenvima...Verzenio."

Medicare • Castration-Resistant Prostate Cancer • Endometrial Cancer • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Renal Cell Carcinoma • Thyroid Gland Carcinoma

Genomic alterations and their pathologic responses in high-risk localized prostate cancer (HRLPC) in subprotocol 1 of the Genomic Umbrella Neoadjuvant study (GUNS). (ASCO-GU 2025) - P2 | "After 8 weeks of LHRHa + apalutamide (APA), participants are assigned to 1 of 4 sub-protocols (SP) combining 16 weeks of an ARPI doublet with drugs defined by specific genomic alterations (e.g. SP-2, docetaxel for RB1, PTEN, TP53 loss; SP-3, niraparib for DNA-repairdef; SP-4, atezolizumab for mismatch-repairdef). SP-1 randomises men without these aggressive genomicalt and includes those that enhance AR activity (ETS fusions, FOXA1, SPOP) to either SP-1a (LHRHa + APA) or SP-1b (LHRHa + APA + abiraterone acetate/prednisone)... SP-1 associated genomicalt (ETS fusion, FOXA1, SPOP) are the most frequent alterations in GUNS. Significantly higher rates of MRD in SP-1 patients treated with an ARPI triplet vs. doublet are of interest and support further evaluation with 2nd stage expansion."

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2 • FOXA1 • PTEN • RB1 • SPOP • TP53

First interim efficacy analysis of the phase I/II PETRANHA trial of saruparib + androgen receptor pathway inhibitors (ARPI) in patients (pts) with metastatic prostate cancer (mPC) (ESMO 2025) - P1/2 | "Methods Pts, allocated by investigator choice, received saruparib 60 mg once daily (OD) + enzalutamide 160 mg OD (Arm 1), abiraterone 1000 mg OD + 5 mg prednisone OD or twice daily (BD; Arm 2), or darolutamide 600 mg BD (Arm 3) until disease progression or intolerable adverse event (AE)...Arm 4 (+ apalutamide 240 mg OD) is ongoing dose escalation and was not included in this analysis...EvoPAR-01 is an ongoing phase 3 study evaluating this combination in mCSPC. Table: 2384MO mCRPC Prior ARPI N=19 mCRPC ARPI-naïve N=31 mCSPC N=27 Median duration of saruparib / ARPI exposure, months (range) 5.5 (1.2–17.7) / 5.5 (1.1–17.7) 14.7 (0.3–24.8) / 15.7 (0.4–24.8) 17.8 (0.2–28.2) / 19.7 (0.2–28.2) Any AE, n (%) 18 (94.7) 31 (100) 26 (96.3) Any AE causally related to saruparib, n (%) 16 (84.2) 28 (90.3) 23 (85.2) Any AE Gr ≥3, n (%) 6 (31.6) 16 (51.6) 14 (51.9) Any serious AE, n (%) 4 (21.1) 10 (32.3) 4 (14.8) Saruparib / ARPI discontinuation due to AE, n (%) 1 (5.3) / 1..."

Clinical • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

Statin use and outcomes in advanced prostate cancer:Secondary analysis of the SPARTAN trial. (PubMed, Urol Oncol) - "In this secondary analysis of the SPARTAN trial, statin use was not associated with improved survival outcomes overall. However, a significant interaction was observed, with statin use linked to worse metastasis-free survival in the placebo arm. These findings suggest a hypothesized interplay between statins and androgen receptor inhibition that warrants further prospective investigation."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

SATURN: Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Safety and tolerability of relugolix in combination with abiraterone or apalutamide for treatment of advanced prostate cancer: Data from a 52-week clinical trial. (ASCO-GU 2025) - P1 | "REL used in combination with ABI or APA showed safety profiles consistent with individual drugs over 52 wks. REL levels were stable, and testosterone was sustained below castration level. These findings support the safety and tolerability of REL combination therapy with ABI or APA for aPC."

Clinical • Combination therapy • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer. (PubMed, Target Oncol) - P1 | "Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs."

Journal • Metastases • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor