Background

The prostate cancer (PC) registry (UFO) has been established with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome in Asia. The registry will also collect patient-reported treatment outcomes and underlying reasons for clinical decision-making.

Methods

This is a large multi-national, observational registry of PC patients presenting to tertiary care hospitals in China, India, Japan, Malaysia, Singapore, South Korea, Taiwan and Thailand. Patients with existing or newly diagnosed high-risk localized PC (HRL), non-metastatic biochemically recurrent PC (M0), or metastatic PC (M1), are being consecutively enrolled and followed for up to 5 years. Quality of life is assessed using EQ5D and FACT-P. The first interim analysis includes 2,063 patients enrolled from study start (15 Sept 2015) until 17 May 2017.

Results

At diagnosis, 56% of all patients had extra-capsular extension of their tumor, 28% had regional lymph node metastasis and 53% had distant metastases. Treatment of M1 patients was mainly with combined androgen blockade (58%) or androgen deprivation therapy (32%) (Table). At enrolment, 97% of M1 patients had ECOG 0-2, 83% reported no or slight pain or discomfort, >84% reported no or slight problems with mobility, dressing or washing, or usual activities, and 92% reported no or slight anxiety and depression. Mean EQ5D visual analogue score was 74.6-79.6 across cohorts. Of 346 M1 patients who reported use of pain medications, 73% used simple analgesics and 36% used weak opioid analgesics for symptom control.

Conclusions

More than 50% of patients diagnosed with PC in our study presented with advanced disease. Few patients reported pain, significant functional impairment or use of strong analgesics.Table: 212O

Characteristics of patients with prostate cancer

Editorial acknowledgement

Writing assistance was provided by Joanne Wolter, Independent on behalf of Janssen.

Clinical trial identification

NCT02546908. Registry Identifier: NOPRODPCR4001.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

R. Kanesvaran: Grants, personal fees: J&J, outside the submitted work. H. Uemura: Grants: Janssen, Astellas, Takeda, AstraZeneca; Personal fees: AstraZeneca, Astellas, Sanofi; Other from Sanofi, outside the submitted work. E. Chiong: Institutional grants: Janssen during the conduct of the study; Honoraria, conference support: Janssen outside the submitted work. Y. Liu: Employee: Janssen Research and Development, LLC; Holds stock: J&J M. Asinas-Tan: Employee: Johnson and Johnson Pte Ltd. W. Liu: Employee: Johnson & Johnson (China) Investment Ltd.,. G.K.M. Low: Employee: Janssen Asia Pacific, Medical affairs; Holds stock: J&J. M. van Kooten Losio: Employee: Johnson and Johnson Pte Ltd; Holds stock: J&J. All other authors have declared no conflicts of interest.

Background

SPARTAN was a global, phase 3 study that evaluated the efficacy and safety of APA vs placebo (PBO) in pts with high-risk nmCRPC, with significant improvement observed in the primary end point (metastasis-free survival; MFS) with APA (Smith, N Engl J Med 2018). Because studies of some targeted agents have demonstrated differences in outcomes among Asian (AS) compared with non-Asian (nAS) pts, we conducted a post hoc analysis of efficacy and safety of APA in the AS subpopulation of pts enrolled in SPARTAN.

Methods

SPARTAN included 1207 pts with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months. Pts were randomized 2:1 to APA (240 mg/d) or PBO added to androgen deprivation therapy. Pts treated in Japan, Taiwan, and South Korea were classified as AS. Baseline characteristics, MFS, PSA, and safety were evaluated for differences between AS and nAS pts.

Results

In the APA and PBO arms, respectively, 83 and 43 pts were AS; 723 and 358 were nAS. Most baseline characteristics were similar between AS and nAS pts; however, AS pts had lower body weight and were more likely to have N1 disease (APA arm) and Gleason score > 7 than nAS pts (Table). Median time from diagnosis to treatment (Tx) was shorter among AS pts than nAS pts. The magnitude of improvement in MFS with APA vs PBO was similar for AS (HR 0.29, P < 0.001) and nAS (HR 0.28, P < 0.0001) pts. A confirmed PSA response was observed in 82% vs 91% (AS vs nAS). No meaningful differences were observed in treatment-emergent adverse events (TEAEs) in AS vs nAS pts, except for rash (38% vs 22%). Tx discontinuations due to TEAEs were higher in Asian pts.

Conclusions

APA had a similar clinical benefit and manageable safety profile among AS and nAS pts with nmCRPC despite AS pts having higher risk characteristics at baseline.Table: 213O

Editorial acknowledgement

Writing assistance was provided by Brian Haas, PhD, of Parexel, and was funded by Janssen Global Services, LLC.

Clinical trial identification

NCT01946204.

Legal entity responsible for the study

Janssen R&D; Rosemary Long, RPh, MBA, Director, Global Medical Affairs Strategic Operations, Janssen Global Services, LLC.

Funding

Janssen Research & Development.

Disclosure

P. Mainwaring: Personal fees: XING Technologies P/L, Ipsen, Janssen, Novartis, Pfizer, Roche; Grants, personal fees: Merck, outside the submitted work; Patent: XING Technologies P/L pending. H. Uemura: Personal fees: Janssen; Personal fees: Astellas, Takeda, Sanofi, Bayer, AstraZenaca, outside the submitted work. A. Bhaumik, S. Cheng, A. Londhe, A. Lopez-Gitlitz: Employee: Janssen Research and Development; Holds stock: Johnson & Johnson. M. Smith: Reports grants, personal fees: Janssen, during the conduct of the study; Personal fees: Astellas, Bayer, outside the submitted work. All other authors have declared no conflicts of interest.

Background

The genetic analysis of circulating tumor cells (CTCs) will be applied for precision medicine of castration-resistant prostate cancer (CRPC). Previous reports showed that the expression of prostate-specific membrane antigen (PSMA) in prostate cancer tissue correlates with cancer aggressiveness. We explored the possibility of PSMA expression in CTCs as a predictive biomarker for CRPC. We already demonstrated in the ESMO Asia 2017 meeting that PSMA expression in CTCs is significantly associated with poor treatment response and shorter PSA-PFS in 17 CRPC patients. However, our previous study had a small sample size. Therefore, we further investigated the PSMA expression at different treatment phases in a larger cohort of CRPC patients and assessed changes in PSMA expression through treatment courses.

Methods

We analyzed 167 samples from 68 CRPC patients (1-7 samples per patient). We investigated expressions of PSMA, androgen receptor splice variant 7 (AR-V7), androgen receptor (AR), epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) in CTCs. CTC analyses were done by AdnaTest (QIAGEN, Germany). The association between these mRNA expression status and treatment lines was examined.

Results

CTCs were detected in 105 samples (63%). The proportion of mRNA expressions in these CTC-positive 105 samples are as follows: 62% were positive for PSMA, 71% positive for AR, 25% positive for AR-V7, 23% positive for EGFR and 37% positive for PD-L1. Among 105 CTC-positive samples, 44 of them derived from patients undergoing pre 1^st-line/1^st-line therapy for CRPC, while 61 samples derived from patients receiving 2^nd-line/more. PSMA, AR and AR-V7 were significantly more expressed in samples from patients receiving 2^nd-line/more therapy (P < 0.05).

Conclusions

We demonstrated that PSMA, AR and AR-V7 were significantly more expressed in CTCs derived from heavily treated patients. Our results suggested that not only aberrant AR expressions such as AR-V7 but also PSMA is indicative of some treatment-resistant mechanisms.

Legal entity responsible for the study

Juntendo University Graduate School of Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Cabozantinib, an inhibitor of MET, AXL and VEGF receptors, is approved for the treatment of patients with advanced renal cell carcinoma, based on findings from the METEOR (NCT01865747) and CABOSUN (NCT01835158) trials. Here, we report the pharmacokinetics (PK) of cabozantinib in Asian and non-Asian populations.

Methods

A population PK analysis was performed using data from nine cabozantinib studies (three Phase I, two Phase II and four Phase III) that included healthy volunteers and patients with various cancer types (including patients from METEOR). The impact of selected covariates (age, weight, sex, ethnicity, and cancer type) on PK parameters was evaluated. Steady-state PK parameters are presented for Asian and non-Asian participants.

Results

Data from 1534 participants were included (patients with cancer, n = 1394; healthy volunteers, n = 140), of whom 46 were of Asian ethnicity and 1488 of non-Asian ethnicity. Metastatic medullary thyroid cancer type had the largest effect on cabozantinib PK parameters, leading to a greater than 90% increase in apparent clearance (CL/F) relative to healthy volunteers. Asian ethnicity was estimated to have a small effect on CL/F, with mean (standard deviation) CL/F for Asians and non-Asians of 2.75 (± 1.47) L/h versus 2.93 (± 1.72) L/h, respectively. This corresponds to an 8% decrease in CL/F in Asians compared with non-Asians, a difference which falls within the inter-individual variability in this study and not considered to be clinically meaningful. Other covariates had small-to-moderate effects on cabozantinib PK parameters.

Conclusions

The PK of cabozantinib is similar in individuals of Asian and non-Asian ethnicity. The lack of difference in PK parameters due to ethnicity is consistent with the metabolism of cabozantinib, given that the major metabolic pathway is via cytochrome P450 3A4 which is not prone to genetic polymorphism.

Editorial acknowledgement

Oxford PharmaGenesis.

Clinical trial identification

XL184-001; XL184-010; XL184-020; XL184-201; XL184-203; XL184-301; XL184-306; XL184-307; XL184-308.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

F. Benzaghou, T.X.Q. Nguyen: Employee: Ipsen. All other authors have declared no conflicts of interest.

Background

During recent years, the range of available first line therapies for metastatic renal cell carcinoma (mRCC) has markedly increased. Evidence is limited on the impact of this change in real world practice. Our objectives were to assess the evolution of medical practices on clinical and healthcare outcomes of mRCC patients (pts) by first line therapy up to and after 2010 in the US.

Methods

We conducted a retrospective cohort study of mRCC patient records from the Explorys™ database (IBM Watson Health™). A cohort was created for pts aged ≥18 years, with an mRCC diagnosis from Dec 1980–Jul 2017, treated from the index date (date of first mRCC prescription), with 6 months' continuous prior enrolment. The data cutoff was 10 Aug, 2017. Included pts received first line treatment as recommended in mRCC guidelines. However, death dates before the index date were deemed missing and not used for survival analysis. Descriptive statistics are presented for baseline characteristics, treatment patterns and treatment duration. Overall survival (OS) was estimated by Kaplan-Meier methods (using time from index date to death/last follow up). Results are reported for index dates in 2005–10 and 2011–17.

Results

1,517 pts were included in the analysis (Table). Sunitinib was the commonest first line therapy in both groups, though median treatment duration was shorter in 2011–17 than 2005–10, and pazopanib was the second most common choice in 2011–17. Median OS was 12 and 24 months for 2005–10 and 2011–17, respectively.Table: 233O

Conclusions

Though these two periods of mRCC pts were broadly similar at baseline, we observed longer median OS, increased pazopanib use, and reduced bevacizumab use as first line therapy in the 2011–17 group, compared with 2005–10. These results are evidence that the rise in available mRCC therapies has been fulfilling an unmet need.

Editorial acknowledgement

Writing and editorial assistance were provided by Lucy Berry of Costello Medical, Cambridge, UK, and funded by Ipsen.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

F. Benzaghou, A. Ren, M. del Pilar Schneider, J. Dinet, E. Pham: Employee: Ipsen.