apalutamide / Generic mfg. - LARVOL DELTA

An Expedition of FDA-Approved Anticancer Drugs in 2024: Synthetic Routes, Mechanisms of Action, and Clinical Indications. (PubMed, Curr Top Med Chem) - "Among the small molecules, kinase inhibitors such as Ribociclib, Imatinib Mesylate, and Nilotinib Hydrochloride Dihydrate modulate critical signaling cascades, while antimetabolites like Fluorouracil and Pemetrexed Disodium disrupt nucleotide biosynthesis. Other classes include DNA-damaging agents (Mitomycin, Gemcitabine Hydrochloride), immune modulators (Pomalidomide, Lenalidomide), and hormonal antagonists (Abiraterone Acetate, Erleada). The macromolecular therapeutics primarily consist of monoclonal antibody-based agents, such as Keytruda, Tecentriq, and Imfinzi, which enhance immune checkpoint inhibition, and antibody-drug conjugates like Enhertu and Elahere, which deliver cytotoxic payloads with high specificity. This review systematically examines the chemical synthesis, mechanisms of action, and therapeutic indications of these FDAapproved agents, emphasizing their role in improving patient outcomes. By analyzing their structural frameworks and biological targets,..."

FDA event • Journal • Oncology

Exploration of Treatment Effect of Novel Hormone Therapy Combined With Local Treatment Based on PSMA PET/CT Evaluation in mHSCP Patients (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

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

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

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

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

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

Genomic alterations and pathologic responses to neoadjuvant androgen receptor pathway inhibitor (ARPI) doublets vs docetaxel triplets in the Genomic Umbrella Neoadjuvant study (GUNS). (ASCO-GU 2026) - P2 | "After 8 weeks of an ARPI doublet (LHRHa + apalutamide [APA]), men are assigned to 1 of 4 sub-protocols (SP) combining 16 weeks of an ARPI doublet with drugs defined by specific genomic biomarkers. SP-1 enrolls men with AR-associated genomicalt (ETS fusions, FOXA1, SPOP) treated with an ARPI doublet +/- abiraterone... SP-2 associated genomicalt (TP53, PTEN, AKT) comprise 30% of the alterations in GUNS. Significantly higher rates of MRD in SP-2b patients treated with an ARPI-docetaxel triplet are of interest and support further evaluation with 2nd stage expansion of SP-2."

Clinical • Tumor mutational burden • Genito-urinary Cancer • Prostate Cancer • Solid Tumor • BRCA2 • FOXA1 • PTEN • RB1 • SPOP • TMB • TP53

Apalutamide + Abiraterone acetate plus Prednisone (AAP) + Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase 2 Study. (PubMed, Clin Cancer Res) - "Treatment intensification with apalutamide, AAP, ADT and SBRT well-tolerated with limited impact on quality of life. While BCR rates exceed the superiority threshold, outcomes aligned with historical benchmarks, supporting further evaluation of the regimen in prospective trials."

Journal • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

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

Real-world analysis of androgen receptor inhibitors in US patients with nonmetastatic castration-resistant prostate cancer: DEAR-EXT study. (PubMed, Prostate Cancer Prostatic Dis) - P | "Darolutamide demonstrated lower discontinuation rates, longer time to progression, and longer MFS vs other ARIs, highlighting its potential to enhance real-world patient outcomes."

Journal • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

PROTEUS: A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy (clinicaltrials.gov) - P3 | N=2517 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Feb 2026 ➔ Dec 2026

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

Active Surveillance With or Without Apalutamide Treatment in Low Risk Prostate Cancer (clinicaltrials.gov) - P2 | N=93 | Completed | Sponsor: Institut Paoli-Calmettes | Unknown status ➔ Completed | N=206 ➔ 93

Enrollment change • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

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

EXTRA-PC: A phase II trial of masofaniten (EPI-7386) and enzalutamide with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (mHSPC). (ASCO-GU 2026) - P1/2, P2 | "They may help overcome AR resistance mechanisms at the ligand-binding domain (LBD), which is the binding site of currently approved androgen receptor pathway inhibitors (ARPIs) such as enzalutamide, apalutamide, and darolutamide. The triplet combination of masofaniten, enzalutamide, and ADT for mHSPC did show efficacy and had an acceptable safety profile. Dual inhibition of the NTD and LBD of the AR is feasible in this setting."

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

OMAHA-004: Phase 3 trial of CYP11A1 inhibitor opevesostat versus androgen receptor pathway inhibitor (ARPI) switch in participants with metastatic castration-resistant prostate cancer (mCRPC) after a prior ARPI. (ASCO-GU 2026) - P3 | "Prior ARPI plus docetaxel for HSPC is permitted if participants received no more than 6 cycles of docetaxel without radiographic disease progression. Approximately 1314 participants will be randomized 1:1 to opevesostat 5 mg orally twice-daily plus dexamethasone 1.5 mg and fludrocortisone 0.1 mg orally once daily or abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily (if prior enzalutamide, darolutamide, or apalutamide) or enzalutamide 160 mg orally once-daily (if prior abiraterone)...Other secondary end points include time to initiation of first subsequent anticancer therapy or death, objective response rate and duration of response per PCWG3-modified RECIST v1.1 by BICR, time to pain progression; time to prostate-specific antigen (PSA) progression, PSA response rate, time to first symptomatic skeletal-related event, and safety and tolerability. Enrollment is ongoing."

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

Real-world effectiveness of systemic therapies after 177Lu]Lu-PSMA-617 (177Lu-PSMA-617) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC): A prostate cancer disease observation (PRECISION) data platform analysis. (ASCO-GU 2026) - "Systemic therapies included ARPIs (abiraterone, enzalutamide, darolutamide, apalutamide); chemotherapy (cabazitaxel, docetaxel, carboplatin, cisplatin, etoposide, mitoxantrone); immunotherapy (pembrolizumab, sipuleucel-T); poly (ADP-ribose) polymerase (PARP) inhibitors (niraparib, olaparib, talazoparib, rucaparib); and radium-223. In this real-world analysis, meaningful clinical responses were observed in a subset of patients who received subsequent systemic therapies after 177Lu-PSMA-617."

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Evaluating the incidence of thrombosis in patients with concurrent second-generation androgen receptor inhibitor therapy and direct oral anticoagulants: A retrospective chart review. (PubMed, J Oncol Pharm Pract) - "This study suggests that there is not an increased incidence of VTE or stroke when compared to historical controls. This study may help clinicians make risk benefit decisions regarding concurrent therapies."

Journal • Retrospective data • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Ischemic stroke • Oncology • Prostate Cancer • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Thrombosis