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Article ; Online: The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment combinations.

Teply, Benjamin A / Antonarakis, Emmanuel S

Expert review of clinical pharmacology

2022 Volume 15, Issue 11, Page(s) 1293–1304

Abstract: Introduction: PARP inhibition in prostate cancer has become a standard-of-care option for men with metastatic castration-resistant prostate cancer (mCRPC) with deficiency in homologous recombination repair (HRRd). The benefit varies based upon the ... ...

Abstract	Introduction: PARP inhibition in prostate cancer has become a standard-of-care option for men with metastatic castration-resistant prostate cancer (mCRPC) with deficiency in homologous recombination repair (HRRd). The benefit varies based upon the characteristics of the PARP inhibitor used and the underlying HRR defect. Optimal patient selection remains a clinical challenge, and investigations are underway to identify effective combination therapies to expand the population that benefits. Areas covered: We review the clinical development of the FDA-approved PARP inhibitors olaparib and rucaparib. Additionally, we explore the status of other PARP inhibitors that remain experimental in prostate cancer, based upon review of published abstracts, articles, and clinicaltrials.gov. Most new studies, including phase 3 trials for talazoparib and rucaparib, involve combinations with novel androgen receptor signaling inhibitors. We review the landscape of emerging PARP inhibitor-based combination therapies. Expert opinion: For men with
MeSH term(s)	Humans ; Male ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; DNA Repair ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology ; Clinical Trials, Phase III as Topic
Chemical Substances	Antineoplastic Agents ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2022-11-02
Publishing country	England
Document type	Review ; Journal Article
ISSN	1751-2441
ISSN (online)	1751-2441
DOI	10.1080/17512433.2022.2140656
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Article ; Online: A case of metastatic adenoid cystic (basal cell) carcinoma of the prostate: Systemic therapy for a rare disease.

Trinh, Jonathan Q / Lele, Subodh M / Teply, Benjamin A

The Prostate

2023 Volume 83, Issue 8, Page(s) 814–819

Abstract: Background: Metastatic adenoid cystic (basal cell) carcinoma of the prostate is an exceedingly rare disease entity. As a result, no current consensus exists for optimal systemic therapy.: Methods: We present a patient with metastatic adenoid cystic ( ... ...

Abstract	Background: Metastatic adenoid cystic (basal cell) carcinoma of the prostate is an exceedingly rare disease entity. As a result, no current consensus exists for optimal systemic therapy. Methods: We present a patient with metastatic adenoid cystic (basal cell) carcinoma of the prostate who subsequently received systemic treatment, including chemotherapy and immunotherapy. We comprehensively reviewed all published data on therapy outcomes in advanced disease. Results: Our patient benefited from combination chemotherapy (carboplatin and paclitaxel), with objective radiographic response and reduction in cancer-related pain. However, chemotherapy was stopped due to cumulative neurotoxicity, and subsequent immunotherapy with atezolizumab did not produce any response. Our literature review revealed inconsistent outcomes with various treatments but showed most promise with chemotherapy. Targeted therapy and immunotherapy seem to benefit specific cases, and androgen deprivation therapy had minimal evidence of benefit. Conclusion: Based on the findings of our case report and literature review, we suggest platinum-based chemotherapy doublets as first-line treatment for metastatic cases of adenoid cystic (basal cell) carcinoma of the prostate, reserving targeted therapy or immunotherapy for select cases based upon molecular profiles.
MeSH term(s)	Male ; Humans ; Prostate/pathology ; Androgen Antagonists ; Rare Diseases ; Adenoids/pathology ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/pathology ; Carcinoma, Adenoid Cystic/diagnostic imaging ; Carcinoma, Adenoid Cystic/drug therapy ; Carcinoma, Basal Cell/pathology ; Skin Neoplasms
Chemical Substances	Androgen Antagonists
Language	English
Publishing date	2023-03-26
Publishing country	United States
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24521
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Zs.A 1608: Show issues

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Article ; Online: Association of plasma NRP2 and VEGF-C levels with prostate cancer disease severity.

Mullen, Sarah A / Das, Dipanwita / Ziamiavaghi, Negin / High, Robin / Datta, Kaustubh / Teply, Benjamin A

The Prostate

2023 Volume 84, Issue 3, Page(s) 277–284

Abstract: Background: Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue ...

Abstract	Background: Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue biopsy specimens collected at diagnosis may have limited utility in identifying patients at highest risk for morbidity and mortality. Given that metastatic tissue is only occasionally obtained for analysis, there is a need for development of a plasma biomarker indicative of NRP2 pathway activation to potentially inform prostate cancer prognosis. Therefore, we investigated if plasma levels of NRP2 or vascular endothelial growth factor C (VEGF-C), a known soluble ligand of NRP2, are prognostic for prostate cancer. We hypothesized that plasma NRP2 and VEGF-C would be associated with more advanced disease or relapsed disease. Methods: NRP2 and VEGF-C levels were quantified by enzyme-linked immunoassay in plasma samples obtained from 145 prostate cancer patients in an opportunistic biobank. These patients were either (1) newly diagnosed (N = 28), (2) in remission (N = 56), or (3) relapsed disease (N = 61). Plasma samples from 15 adult males without known malignancy served as a comparator cohort. Statistical analysis was performed to investigate the association of plasma NRP2/VEGF-C with patient outcomes, adjusting for age, race, prostate-specific antigen (PSA), Gleason score, and tumor stage at diagnosis. Results: Neither NRP2 nor VEGF-C levels were significantly different in cancer patients compared to noncancer controls. We observed no clear association between plasma NRP2 and disease severity. Increased plasma VEGF-C was significantly associated with disease remission and correlated with Stage I/II and intermediate-risk Gleason score. Neither NRP2 nor VEGF-C correlated with PSA level. Conclusions: Although tissue NRP2 expression correlates with severe disease, this was not observed for plasma NRP2. Plasma NRP2 levels did not correlate with disease severity or relapse. VEGF-C was highest in patients in remission and with less severe disease. Future investigation is needed to identify noninvasive methods to assess tumor NRP2 status.
MeSH term(s)	Adult ; Humans ; Male ; Neoplasm Recurrence, Local ; Neuropilin-2/metabolism ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology ; Vascular Endothelial Growth Factor C
Chemical Substances	Neuropilin-2 ; Prostate-Specific Antigen (EC 3.4.21.77) ; Vascular Endothelial Growth Factor C ; VEGFC protein, human ; neuropilin-2, human
Language	English
Publishing date	2023-11-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24648
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Article: Biomarkers for Treatment Response in Advanced Prostate Cancer.

Asif, Samia / Teply, Benjamin A

Cancers

2021 Volume 13, Issue 22

Abstract: Multiple treatment options with different mechanisms of action are currently available for the management of metastatic prostate cancer. However, the optimal use of these therapies-specifically, the sequencing of therapies-is not well defined. In order ... ...

Abstract	Multiple treatment options with different mechanisms of action are currently available for the management of metastatic prostate cancer. However, the optimal use of these therapies-specifically, the sequencing of therapies-is not well defined. In order to obtain the best clinical outcomes, patients need to be treated with the therapies that are most likely to provide benefit and avoid toxic therapies that are unlikely to be effective. Ideally, predictive biomarkers that allow for the selection of the therapies most likely to be of benefit would be employed for each treatment decision. In practice, biomarkers including tumor molecular sequencing, circulating tumor DNA, circulating tumor cell enumeration and androgen receptor characteristics, and tumor cell surface expression (PSMA), all may have a role in therapy selection. In this review, we define the established prognostic and predictive biomarkers for therapy in advanced prostate cancer and explore emerging biomarkers.
Language	English
Publishing date	2021-11-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13225723
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Article ; Online: Current Management of Refractory Germ Cell Tumors.

Abughanimeh, Omar / Teply, Benjamin A

Current oncology reports

2021 Volume 23, Issue 9, Page(s) 101

Abstract: Purpose of review: Germ cell tumors (GCTs) are the most common solid tumors affecting men between ages of 20 and 34 years. Most of the cases, even in advanced disease, will have good prognosis. However, around 20-30% of advanced disease will be ... ...

Abstract	Purpose of review: Germ cell tumors (GCTs) are the most common solid tumors affecting men between ages of 20 and 34 years. Most of the cases, even in advanced disease, will have good prognosis. However, around 20-30% of advanced disease will be refractory or develop relapse after treatment. Herein, we review the current management of refractory/relapsed GCTs. Recent findings: Salvage treatment of GCTs has been a controversial topic for the last few decades. Conventional dose chemotherapy (CDCT), high-dose chemotherapy (HDCT) with stem cell infusion, and surgical salvage were proven to be effective and curative options in some cases. The international randomized trial (TIGER) will ultimately answer which chemotherapy approach may be optimal. Furthermore, the usage of immunotherapy is still under investigation with limited data so far in the setting of relapsed/refractory GCTs. Curative paradigms including with CDCT and HDCT are possible, although novel approaches beyond HDCT are still needed to eliminate mortality from this disease.
MeSH term(s)	Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Humans ; Male ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Neoplasms, Germ Cell and Embryonal/pathology ; Prognosis ; Salvage Therapy/methods ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/pathology ; Young Adult
Language	English
Publishing date	2021-07-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057359-5
ISSN	1534-6269 ; 1523-3790
ISSN (online)	1534-6269
ISSN	1523-3790
DOI	10.1007/s11912-021-01093-z
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Zs.A 5521: Show issues

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Article: Targeting treatment options for castration-resistant prostate cancer.

Miller, Dannah R / Ingersoll, Matthew A / Teply, Benjamin A / Lin, Ming-Fong

American journal of clinical and experimental urology

2021 Volume 9, Issue 1, Page(s) 101–120

Abstract: Prostate cancer (PCa) is the most commonly diagnosed solid tumor and the second leading cause of cancer-related deaths in U.S. men in 2020. Androgen-deprivation therapy (ADT) is the standard of care for metastatic PCa. Unfortunately, PCa relapse often ... ...

Abstract	Prostate cancer (PCa) is the most commonly diagnosed solid tumor and the second leading cause of cancer-related deaths in U.S. men in 2020. Androgen-deprivation therapy (ADT) is the standard of care for metastatic PCa. Unfortunately, PCa relapse often occurs one to two years after initiation of ADT, resulting in the development of castration-resistant PCa (CRPCa), a lethal disease. While several anticancer agents such as docetaxel, abiraterone acetate, and enzalutamide are currently utilized to extend a patient's life after development of CRPCa, patients will eventually succumb to the disease. Hence, while targeting androgen signaling and utilization of docetaxel remain the most crucial agents for many of these combinations, many studies are attempting to exploit other vulnerabilities of PCa cells, such as inhibition of key survival proteins, anti-angiogenesis agents, and immunotherapies. This review will focus on discussing recent advances on targeting therapy. Several novel small molecules will also be discussed.
Language	English
Publishing date	2021-02-15
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2330-1910
ISSN	2330-1910
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Article ; Online: Anticipating the Next Challenging Clinical Dilemmas in Prostate Cancer.

Krishnan, Mridula / Teply, Benjamin A

JCO oncology practice

2020 Volume 16, Issue 12, Page(s) 791–792

MeSH term(s)	Humans ; Male ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/therapy
Language	English
Publishing date	2020-12-11
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.20.00908
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Zs.A 7198: Show issues

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Article: Diagnosis of Metastatic Non-Small Cell Lung Cancer during Hospitalization: Missed Opportunity for Optimal Supportive Care?

Upadhyay Banskota, Shristi / Trinh, Jonathan Q / Lyden, Elizabeth / Houlihan, Conor / Asif, Samia / Abughanimeh, Omar / Teply, Benjamin A

Cancers

2024 Volume 16, Issue 6

Abstract: Purpose: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative ... ...

Abstract	Purpose: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. Patients and methods: We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). Results: Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. Conclusion: Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients.
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16061221
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Article ; Online: Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma: A case report of abscopal toxicities.

Huynh, Linda My / Bonebrake, Benjamin T / DiMaio, Dominick J / Baine, Michael J / Teply, Benjamin A

Medicine

2022 Volume 100, Issue 49, Page(s) e28199

Abstract: Rationale: Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While ... ...

Abstract	Rationale: Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT. Patient concerns: We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk. Diagnosis: DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later. Interventions: Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week. Outcomes: A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient's sites of disease, both in- and out-field, have remained responsive to treatment. Lessons: Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.
MeSH term(s)	Aged ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Carcinoma, Renal Cell/drug therapy ; Doxycycline/therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Humans ; Kidney Neoplasms/drug therapy ; Lung Neoplasms/radiotherapy ; Male ; Nivolumab/adverse effects ; Nivolumab/therapeutic use ; Pemphigoid, Bullous/drug therapy ; Pemphigoid, Bullous/etiology ; Prednisone/therapeutic use ; Radiation Injuries ; Treatment Outcome
Chemical Substances	Antineoplastic Agents, Immunological ; Nivolumab (31YO63LBSN) ; Doxycycline (N12000U13O) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000028199
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Article: Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer.

Vieira, Heidi M / Kasper, David P / Wang, Runqiu / Smith, Lynette M / Enke, Charles A / Bergan, Raymond C / Teply, Benjamin A / Baine, Michael J

Radiation oncology journal

2023 Volume 41, Issue 3, Page(s) 154–162

Abstract: Purpose: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and ...

Abstract	Purpose: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting. Materials and methods: We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation. Results: The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533). Conclusion: Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making.
Language	English
Publishing date	2023-09-21
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2712565-8
ISSN	2234-3156 ; 2234-1900
ISSN (online)	2234-3156
ISSN	2234-1900
DOI	10.3857/roj.2023.00262
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