Metastatic non-small cell lung cancer presenting with an orbital metastasis: a case report

Metastatic disease to the orbit occurs in up to 7% of cancers. In approximately 20% of cases, there is no diagnosis of cancer at the time of presentation with orbital metastatic disease. This is a case of a 53-year-old female smoker whose initial presentation of metastatic non-small cell lung cancer was with an orbital metastasis

Dexamethasone-induced flares of Trichophyton rubrum masquerading as docetaxel cutaneous toxicity: a case report

Docetaxel chemotherapy is increasingly used in the treatment of castration-resistant prostate cancer. Cutaneous toxicity is common with docetaxel, occurring in up to 75% of cases. We present an unusual case of castration-resistant prostate cancer in which our patient developed recurrent but transient episodes of skin rash following each cycle of docetaxel. Initially, the rash was attributed to docetaxel cutaneous toxicity however a microbiological diagnosis of Trichophyton rubrum was subsequently made. We postulated that dexamethasone pre-medication transiently suppressed anti-fungal immunity, and indeed further flares were prevented by significantly reducing the dose of dexamethasone while continuing treatment with docetaxel

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer

PARP inhibitor; Androgen receptor; EnzalutamideInhibidor de PARP; Receptor de andrógenos; EnzalutamidaInhibidor de PARP; Receptor d'andrògens; EnzalutamidaPoly(ADP-ribose) polymerase inhibitors in combination with androgen-receptor signaling inhibitors are a promising therapeutic option for patients with metastatic castration-sensitive prostate cancer (mCSPC) and homologous recombination repair (HRR) gene alterations. Here, we describe the design and rationale of the multinational, phase III, TALAPRO-3 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide in patients with mCSPC and HRR gene alterations. The primary end point is investigator-assessed radiographic progression-free survival (rPFS) per RECIST 1.1 in soft tissue, or per PCWG3 criteria in bone. The TALAPRO-3 study will demonstrate whether the addition of talazoparib can improve the efficacy of enzalutamide as assessed by rPFS in patients with mCSPC and HRR gene alterations undergoing androgen deprivation therapy. Clinical Trial Registration:NCT04821622 (ClinicalTrials.gov) Registry Name: Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC. Date of Registration: 29 March 2021.This study was sponsored by Pfizer. Astellas Pharma Inc. provided enzalutamide

The TALAPRO-3 study design: a plain language summary

Resumen; Cáncer de próstata metastásicoSummary; Metastatic prostate cancerResum; Càncer de pròstata metastàticWhat is this summary about?: This summary is about the ongoing research study called TALAPRO-3. This study is testing the use of two medicines called talazoparib and enzalutamide. The two medicines are being used together as a treatment for patients with a type of cancer called metastatic castration-sensitive prostate cancer and changes in specific DNA repair genes within their tumors. The study began in May 2021, and includes 599 patients from 27 countries. What is metastatic castration-sensitive prostate cancer?: Metastatic castration-sensitive prostate cancer is known as mCSPC for short. It is cancer that has started in the prostate and spread to other body parts. The prostate is a gland below the bladder and helps make semen (the liquid that contains sperm). Castration-sensitive means that the cancer responds to treatments that lower testosterone in the blood. Which medicines are being tested?: In this study, some patients will take talazoparib plus enzalutamide while others will take a placebo plus enzalutamide. Talazoparib and enzalutamide are two different cancer medicines. Talazoparib is not currently used to treat patients with mCSPC. Enzalutamide is used to treat patients with prostate cancer. Talazoparib plus enzalutamide is being compared with a placebo plus enzalutamide to see if patients live longer without their cancer getting worse, or them dying, when taking talazoparib plus enzalutamide or when taking a placebo plus enzalutamide. What are the aims of the talapro-3 study?: This study aims to find out if treatment with talazoparib plus enzalutamide increases the length of time the patients in the study live without their cancer getting worse, or them dying, compared with treatment with a placebo plus enzalutamide. The study will also measure how long the patients in the study live, the number and types of side effects they have, their general health and quality of life, and whether there are changes in how patients report their pain.Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov).The TALAPRO-3 trial is sponsored by Pfizer Inc. Astellas Pharma Inc. is providing enzalutamide

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design

PARP inhibitor; Androgen receptor; EnzalutamideInhibidor de PARP; Receptor d'andrògens; EnzalutamidaInhibidor de PARP; Receptor de andrógenos; EnzalutamidaPARP inhibitors in combination with androgen receptor-targeted therapy have demonstrated potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Here, we describe the design and rationale of the multinational, phase III, two-part TALAPRO-2 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide as a first-line treatment for patients with mCRPC with or without DNA damage response (DDR) alterations. This study has two co-primary end points: radiographic progression-free survival (rPFS) by blinded independent clinical review in all-comers (cohort 1) and in patients with DDR alterations (cohort 2). TALAPRO-2 will demonstrate whether talazoparib plus enzalutamide can significantly improve the efficacy of enzalutamide in terms of rPFS in both molecularly unselected and DDR-deficient patients with mCRPC (NCT03395197)

Plain language summary of the results from the TALAPRO-2 study: Talazoparib plus enzalutamide versus placebo plus enzalutamide for patients with advanced prostate cancer

Genetics; Metastasis; ProstateGenética; Metástasis; PróstataGenètica; Metàstasi; PròstataWhat is this summary about?: This summary describes the results from the TALAPRO-2 research study (also known as a clinical trial). The TALAPRO-2 study tested the combination of two medicines called talazoparib plus enzalutamide. This combination of medicines was used as the first treatment for adult patients with metastatic castration-resistant prostate cancer. The combination of talazoparib plus enzalutamide was compared with a placebo plus enzalutamide. What is metastatic castration-resistant prostate cancer?: Metastatic castration-resistant prostate cancer is a type of cancer that starts in the prostate and has spread to other parts of the body. Castration-resistant means that the cancer continues to grow even when testosterone levels in the blood are reduced to very low levels. Taking medicines to lower testosterone levels in the blood is a standard treatment for men with advanced prostate cancer. What are the aims of the talapro-2 trial?: TALAPRO-2 looked at if combining talazoparib plus enzalutamide would increase the length of time patients lived before their cancer got worse or they died compared with a placebo plus enzalutamide. Researchers looked at how treatment affected the size and number of tumors and the length of time before patients needed to change to a new cancer medicine. Researchers also looked at any side effects patients had during the study. What are the key takeaways?: A total of 805 patients with metastatic castration-resistant prostate cancer took part in the study. Compared with patients who took a placebo plus enzalutamide, the group of patients who took talazoparib plus enzalutamide had a 37% reduced risk of their cancer getting worse or dying. Some patients had tumors that at the start of the study could be measured with scans. Sixty-two percent of patients who took talazoparib plus enzalutamide had their tumors decrease or shrink to the point that they could no longer be seen on scans versus 44% of patients who took a placebo plus enzalutamide. Patients who took talazoparib plus enzalutamide were more likely to have a longer time before they needed to change to a new cancer medicine. The most common side effects of talazoparib plus enzalutamide were low levels of red blood cells (66% of patients) and neutrophils (36% of patients), and excessive tiredness or exhaustion (34% of patients).Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov).The TALAPRO-2 trial is sponsored by Pfizer Inc. Astellas Pharma Inc. is providing enzalutamide

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer

Atezolizumab; Cabozantinib; Immune checkpoint inhibitorAtezolizumab; Cabozantinib; Inhibidor del punto de control inmunitarioAtezolizumab; Cabozantinib; Inhibidor del punt de control immunitariCabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy – a population with a significant unmet need for treatment options.This study is funded by Exelixis but includes support (including the provision of atezolizumab) from Roche

First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial

Talazoparib; Cáncer de próstata metastásico resistente a la castraciónTalazoparib; Metastatic castration-resistant prostate cancerTalazoparib; Càncer de pròstata metastàtic resistent a la castracióPreclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N = 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N = 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population (N = 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P < 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P = 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197.This study was sponsored by Pfizer Inc. Astellas Pharma Inc. provided enzalutamide. The authors wish to thank L. Yu and the Pfizer Clinical Programming team. Editorial and medical writing support was provided by A. Smith and E. Messina on behalf of CMC Affinity, a division of IPG Health Medical Communications, and was funded by Pfizer

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer

Clinical trial; Enzalutamide; TalazoparibEnsayo clínico; Enzalutamida; TalazoparibAssaig clínic; Enzalutamida; TalazoparibWhat is this summary about? This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing the combination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in December 2017 and has enrolled 1037 adult men with metastatic castration-resistant prostate cancer from 26 countries. What is metastatic castration-resistant prostate cancer? Metastatic castration-resistant prostate cancer is a type of cancer that has advanced beyond the prostate and continues to grow even when testosterone levels in the blood are suppressed. Which medicines are being tested? The combination of talazoparib plus enzalutamide will be compared with enzalutamide plus placebo. Enzalutamide is approved to treat men with prostate cancer. Talazoparib is not approved to treat men with prostate cancer. A placebo does not contain any active ingredients and is also known as a sugar pill. What are the aims of the TALAPRO-2 trial? The TALAPRO-2 trial will find out if combining talazoparib with enzalutamide increases the length of time the men in the study live without their cancer getting worse compared with enzalutamide plus placebo. The study will also measure how long men in the study live and any side effects the men have while they are taking the study medicines. Researchers are also testing the DNA from the tumor cells of all men in the study to find out if they have faulty DNA repair genes. Clinical Trial Registration: NCT0339519 (ClinicalTrials.gov