Background

Patients with mCRPC and BRCA alterations have poor outcomes with current standard of care treatments. The phase 3 MAGNITUDE study found that patients with BRCA+ mCRPC benefit from first-line treatment with NIRA+AAP. Here we report results from the second interim analysis (IA2) for the subgroup of patients enrolled in Asia, focusing on BRCA1/2-positive (BRCA+) cohort.

Methods

The subgroup analysis reports updated data for the primary endpoint of radiographic progression-free survival (rPFS) by blinded independent central review (BICR). Additionally, the secondary endpoints of time to symptomatic progression (TSP), time to cytotoxic chemotherapy (TCC), and overall survival (OS) in the BRCA+ cohort, time to PSA progression (TPP) in the BRCA+ cohort and safety in the HRR+ cohort are also explored.

Results

The Asian subgroup included 36 BRCA+ pts. In the BRCA+ cohort, improvement in rPFS by BICR was observed with NIRA+AAP (N = 17) vs. PBO+AAP (N = 19), with 71% reduced risk of progression or death (HR, 0.29, 95% CI, 0.11, 0.77) (Table). NIRA+AAP extended median rPFS to 22 mos over 8 mos in PBO+AAP. NIRA+AAP also provided clinically relevant delays in TSP, TCC, and TPP. Although OS data were not mature, OS at 24 months was 66.9% in the NIRA+AAP group and 58.6% in PBO+AAP. In the all HRR+ population from Asia (N = 68), AEs were consistent with known side effects of NIRA and AAP. Grade 3/4 treatment-emergent adverse events (AEs) occurred in 71% in the NIRA+AAP group and 38% in PBO+AAP. Serious AEs were reported for 46% and 33% of pts, respectively, and 14% and 8% had AEs leading to discontinuation of the study drug. Safety results were consistent with IA1, with no new safety signals observed. Table: 258MO

Clinical outcomes in the Asian subgroup with BRCA+ mCRPC

Conclusions

Longer follow-up of the Asian subgroup confirms initial observations of a benefit from NIRA+AAP in BRCA+ mCRPC pts, which is consistent with the overall MAGNITUDE study results.

Clinical trial identification

NCT03748641.

Editorial acknowledgement

Wirting assistance was provided by Joanne Wolter (independent) on behalf of Janssen Asia Pacific.

Legal entity responsible for the study

Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd.

Funding

Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd.

Disclosure

M. Saad: Financial Interests, Personal, Advisory Role: Johnson&Johnson, MSD, AstraZeneca, Novartis, Merck, Bristol Myers Squibb, Viatris, Ipsen; Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Novartis, Johnson&Johnson, Ipsen, Cipla, AstraZeneca, Eisai, Pfizer, Amgen; Financial Interests, Personal, Research Grant: Johnson & Johnson, MSD. K.N. Chi: Financial Interests, Personal, Advisory Role: ESSA, Astellas Pharma, Janssen, Sanofi, Amgen, Bayer, AstraZeneca, Roche, POINT Biopharma, Daiichi Sankyo, Merck, Constellation Pharmaceuticals; Financial Interests, Personal, Expert Testimony: AstraZeneca, Novartis; Financial Interests, Personal, Other, Honoraria: Janssen, Astellas Pharma, Bayer, AstraZeneca, Roche, Merck; Financial Interests, Personal, Research Grant: Janssen, Astellas Pharma, Bayer, Sanofi, Bristol Myers Squibb, Merck, Roche, AstraZeneca, Novartis, Pfizer, ESSA. S.K. Sandhu: Financial Interests, Institutional, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb/Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Merck, Roche/Genentech; Financial Interests, Institutional, Other, Honoraria: Bristol Myers Squibb, Merck, Merck Serono, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Merck, Endocyte/Advanced Accelerator Applications, Genentech/Roche, Novartis. G. Attard: Financial Interests, Personal, Advisory Role: Janssen-Cilag, Veridex, Ventana Medical Systems, Astellas Pharma, Medivation, Novartis, Millennium, Abbott Laboratories, ESSA, Bayer, Pfizer, AstraZeneca, Ferring; Financial Interests, Personal, Speaker’s Bureau: Janssen, Astellas Pharma, Takeda, Sanofi, Ventana Medical Systems, Ipsen, AstraZeneca, Ferring; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen, Astellas Pharma, Medivation, Ventana Medical Systems, Abbott Laboratories, Bayer, ESSA, Pfizer, Ferring; Other, Personal, Other, Immediate family member: Janssen, Astellas Pharma; Financial Interests, Personal, Royalties: Institute of Cancer Research; Financial Interests, Personal, Other, Honoraria: Janssen, Astellas Pharma; Financial Interests, Personal, Advisory Board, Honoraria, Immediate Family Member: Janssen; Financial Interests, Institutional, Research Grant: Janssen, Arno Therapeutics, Innocrin Pharma. P.S.J. Francis, S. Li, S. Dibaj, J. Zhang, W. Kim, A. Lopez-Gitlitz, D. Wu, A. Singh, R. De Vries, L. Zhang: Financial Interests, Personal, Full or part-time Employment: Janssen (Johnson & Johnson); Financial Interests, Personal, Stocks/Shares: Janssen (Johnson & Johnson). All other authors have declared no conflicts of interest.

Background

The treatment landscape of mCSPC has been evolving in the last decade with androgen receptor signaling inhibitors being the preferred life prolonging therapeutic choice. We examined the impact of the starting therapy on clinical outcomes in mCSPC in real-world clinical practice in Japan.

Methods

This retrospective cohort study evaluated treatment patterns and outcomes in adult patients with mCSPC using the Medical Data Vision hospital-based dataset in Japan. All patients with newly diagnosed mCSPC from 1 Jan 2018 to 30 Sept 2022 were enrolled and followed up until 31 Mar 2023. Time to event analyses used Kaplan Meier methods. Risks of death and onset of castration resistance (CR) was estimated using a Cox proportional hazard model adjusted for potential confounding factors (age, BMI, co-morbidities).

Results

16,454 patients with mCSPC were enrolled; 600 (3.6%) started on apalutamide (APA) + androgen-deprivation therapy (ADT), 607 (3.7%) on enzalutamide (ENZ) + (ADT), 945 (5.7%) on abiraterone acetate + prednisone (ABI) +ADT, 253 (1.5%) on docetaxel (DOC) +ADT, 9115 (55.3%) on combined androgen blockade (CAB), 1174 (7.1%) on ADT alone, and 3097 (18.8 %) had radiation therapy. Overall survival and CR-free survival were significantly longer in patients starting with APA + ADT compared to other treatment regimens (p<0.001 for both). In patients with regular PSA assessment available, a higher % of patients starting with APA+ADT achieved PSA50 (p<0.001) and undetectable PSA (≤ 0.2 ng/ml) at 3 months (p<0.001) compared with other treatments after adjusting for age, BMI and CCI. Table: 260MO

Features and clinical outcomes of patients with mCSPC*

Conclusions

ADT/CAB continue to be used widely despite availability of newer life prolonging therapies. This analysis demonstrated that Use of APA + ADT as a starting treatment of mCSPC was associated with significantly better clinical outcomes versus any other life prolonging therapy or traditional CAB in real-world clinical practice in Japan.

Editorial acknowledgement

Writing assistance was provided by Joanne Wolter MBBS, PhD (independent) on behalf of Janssen Global Services LLC.

Legal entity responsible for the study

Janssen Global Services, LLC.

Funding

Janssen Global Services, LLC.

Disclosure

M. Shiota: Financial Interests, Personal, Financially compensated role: Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Sanofi and Bayer Yakuhin; Financial Interests, Personal, Research Funding: Daiichi Sankyo. Yanfang Liu, Suneel Mundle, Xiayi Wang, Mehregan Nematian-Samani. S.D. Mundle, Y. Liu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson LLC; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson LLC. M. Nematian-Samani, J. Hwang, X. Wang: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson LLC.

Background

The CHART trial showcased the survival advantage of rezvilutamide plus androgen deprivation therapy (ADT) over bicalutamide plus ADT in high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients. This post-hoc analysis aims to evaluate the effect of liver and metabolic toxicities on survival outcomes and quality of life (QoL) among high-volume mHSPC patients receiving rezvilutamide.

Methods

In the CHART trial, mHSPC patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide or bicalutamide. Liver toxicity in this post-hoc analysis encompassed elevated γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase or blood bilirubin; metabolic toxicity comprised hypertriglyceridemia, hypercholesterolemia and weight gain. The association between toxicities and survival outcomes and QoL was analyzed.

Results

Among patients treated with rezvilutamide plus ADT, the incidence of liver toxicity and metabolic toxicity was 24.6% and 56.7%, respectively (Table). These toxicities were mostly of grade 1 or 2 and resolved or improved without requiring treatment modification. Patients presenting with metabolic toxicity demonstrated extended progression-free survival (PFS) (HR=0.594, 95%CI 0.400, 0.883, P=0.010) and overall survival (OS) (HR=0.594, 95%CI 0.383, 0.922, P=0.020) than those without. However, no difference in survival was discerned between patients with or without liver toxicity. Notably, patients who developed grade 3 metabolic toxicity displayed superior QoL compared to those without. Table: 261MO

Treatment-related adverse events of special interest (n=323)

Conclusions

To our knowledge, this is the first study to reveal an association between metabolic toxicity and prolonged PFS and OS in mHSPC patients on rezvilutamide plus ADT, leading to an enhanced QoL.

Clinical trial identification

NCT03520478; May 30th, 2018.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The prognostic significance of PSA kinetics after DOC or ABI treatment in Asian mHSPC patients (pts) remains undetermined. We evaluated PSA response to DOC or ABI and its association with survival outcome.

Methods

The medical records of 574 mHSPC pts who received DOC (n = 419) or ABI (n = 155) in addition to androgen-deprivation therapy at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) for pts with and without a deep and rapid PSA decline (≥90% decline in PSA level [PSA90] at 3 months [mo] or undetectable PSA nadir (<0.1 ng/mL) were compared. Survival and hazard ratios (HRs) were estimated using the Kaplan-Meier method and Cox proportional hazard model, respectively.

Results

Median follow-up period was 22.4 (DOC: 23.8; ABI: 17.3) mo. A substantially higher proportion of pts achieved PSA90 with ABI than with DOC at 3 (74% vs 26.2%, p < 0.001) mo. Median time to undetectable PSA nadir was 6.2 (interquartile range: 3.6 – 11.5) mo. At 6 mo, an undetectable PSA nadir was observed in 46.0% and 11.9% of ABI and DOC pts, respectively. Pts who achieved PSA90 at 3 mo had better median PFS (entire cohort: 27.1 vs 14.5 months, p < 0.001, HR = 0.47; DOC: 17.7 vs 13.8 mo, p < 0.001, HR = 0.62; ABI: not reached [NR] vs 29.1 mo, p = 0.03, HR = 0.53) and OS (entire cohort: NR vs 58.5 mo, p < 0.001, HR = 0.43; DOC: NR vs 58.5 mo, p < 0.001, HR = 0.38; ABI: NR vs 43.0 mo, p = 0.01, HR = 0.39). Pts who achieved undetectable PSA nadir also had better median PFS (53.6 vs 13.2 mo, p < 0.001, HR = 0.14) and OS (NR vs 48.4 mo, p < 0.001, HR = 0.13). These associations remained significant for the separate treatment groups (PFS: DOC: 42.5 vs 13.4 mo, p < 0.001, HR = 0.21; ABI: NR vs 11.0 mo, p < 0.001, HR = 0.08; OS: DOC: NR vs 58.5 mo, p < 0.001, HR = 0.09; ABI: NR vs 26.1 mo, p < 0.001, HR = 0.08).

Conclusions

Deep and rapid PSA responses with DOC or ABI in Asian mHSPC patients were associated with significantly improved survival outcome, with potentially valuable prognostic significance for patient management and future trial design.

Editorial acknowledgement

Assistance with statistical analysis and language editing were provided by Best Solution Co. Ltd.

Legal entity responsible for the study

The authors.

Funding

Hong Kong Society of Uro-Oncology.

Disclosure

All authors have declared no conflicts of interest.

Background

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) demonstrated survival improvement for castration-resistant prostate cancer (CRPC). However, which agent is better for non-metastatic CRPC patients remains quite unclear.

Methods

To evaluate which agent is better for CRPC patients as a first-line treatment, an investigator-initiated, multicenter, randomized controlled trial (ENABLE study for PCa) including both metastatic and non-metastatic CRPC was conducted in Japan. We additionally analyzed such as prostate-specific antigen (PSA) response rate (≥50% decline from baseline), overall survival, and safety assessment in non-metastatic CRPC patients.

Results

In 92 patients in each arm treated and analyzed, the number of non-metastatic patients in the ENZ and the ABI arm was 15 and 26, respectively. There was no significant difference in PSA response rate between the ENZ and the ABI arms (80% and 64%, respectively; P = 0.30). There was no significant difference in overall survival between arms (median, not reached and 33.7 months in the ENZ and the ABI arm, respectively; hazard ratio, 1.47; 95% CI, 0.47–4.62; P = 0.53). Furthermore, no significant differences were observed in radiographic progression-free survival and cancer-specific survival between arms (P = 0.61 and P = 0.64, respectively). The number of grade ≥3 of adverse events in the ENZ and the ABI arm were only 4 and 6, respectively.

Conclusions

ABI showed a similar efficacy to ENZ with a similar safety profile in non-metastatic CRPC patients.

Clinical trial identification

UMIN000015529;1 November 2014.

Legal entity responsible for the study

The authors.

Funding

Japanese Foundation for Multidisciplinary Treatment of Cancer.

Disclosure

K. Izumi: Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal and Institutional, Invited Speaker: Janssen Pharmaceutical. A. Mizokami: Financial Interests, Personal, Invited Speaker: Astellas Pharma, Janssen Pharmaceutical. All other authors have declared no conflicts of interest.

Background

Nivolumab with TKI is an accepted treatment option for metastatic RCC (mRCC).However, nivolumab at currently licensed doses remains unaffordable in India where most patients pay out-of-pocket. We evaluated the practice patterns and clinical outcomes with low dose nivolumab combined with TKI in a tertiary academic hospital in India.

Methods

Consecutive mRCC patients treated with nivolumab and TKIs between December 2019 and December 2022 were included. Due to variations in nivolumab dosing frequencies, we used dose/Kg/14 days for comparative analysis. The survival impact of treatment de-escalation due to financial or drug toxicity was evaluated. PFS, OS were calculated as per standard definitions and adverse events graded as per CTCAE4.1.

Results

We identified 57 patients who received nivolumab and TKI with 38(63.2%) IMDC intermediate and 15(26.4%) poor prognoses. The mean age was 53.1±8 years, male (82%), non-clear cell histology in 16(28%). Common metastatic sites were osseous (43.9%), pulmonary (73.7%), CNS 8(10.2%) and Liver15(26.3%). Forty-six (80.7%) received no prior systemic therapy. The median Nivolumab dose was 0.88 mg/kg/14days (IQR0.4-1.4), commonly dosed as 40mg every 21-28 days. The TKIs used were Lenvatinib (47.4%), cabozantinib (49.1%). At 12 months median follow-up, the PFS of 31 patients who received <1mg/kg/14days (ULD) of Nivolumab was 11 months versus 23 months among the 25 patients receiving >1mg/kg/14days (LD) (p=0.39). The median OS was NR vs 25 months (P= 0.51). The one-year PFS and OS was 35.5% vs 42.3% and 45.2% vs 53.8% for ULD vs LD respectively. Most (68.4%) underwent treatment de-escalation due to financial toxicity 28(43.9%) or drug toxicity 11(19.3%) without any detriment to PFS or OS (1year PFS and OS with and without de-escalation was 46% vs 22.2% and 56.4% vs 33.3% respectively). Grade 3&4 adverse events were palmoplantar dysesthesia 10(17.5%), hypertension 8(14%). Primary hypothyroidism 28(52.8%) was the commonest grade 2 AE.

Conclusions

LD nivolumab with TKI did not result in inferior survival although the efficacy of ULD could not be confirmed. Treatment de-escalation due to financial toxicity was common. LD strategies in mRCC warrant prospective trial evaluation.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Platinum-based chemo is the standard of care (SOC) for la/mUC. An unmet need remains as long-term outcomes are poor. Here we present EV-302, a global, phase 3, open-label, randomized study evaluating EV+P in patients (pts) with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemo.

Methods

Pts with previously untreated la/mUC (regardless of PD-L1 expression) were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg; IV) on Days 1 and 8 and P (200 mg; IV) on Day 1 or gemcitabine with cisplatin or carboplatin. Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS. Select secondary endpoints included overall response rate (ORR) and safety.

Results

886 pts (EV+P: 442; chemo: 444) were randomized; pt characteristics were balanced between arms. At data cutoff, median follow-up was 17.2 mo. PFS was significantly prolonged with EV+P vs chemo, reducing the risk of progression or death by 55% (median PFS, 12.5 mo vs 6.3 mo, respectively; HR 0.45 [95% CI: 0.38-0.54]; P<0.00001). OS was significantly prolonged with EV+P vs chemo, reducing the risk of death by 53% (median OS, 31.5 mo vs 16.1 mo, respectively; HR 0.47 [95% CI: 0.38-0.58]; P<0.00001). Confirmed ORR was 67.7% and 44.4% in the EV+P and chemo arms, respectively (P<0.00001). Grade ≥3 TRAEs occurred in 55.9% with EV+P and 69.5% with chemo; most common were maculopapular rash (7.7%), hyperglycemia (5.0%), and neutropenia (4.8%) for EV+P and anemia (31.4%), neutropenia (30.0%), and thrombocytopenia (19.4%) for chemo. Most common (≥5% ) grade ≥3 TRAEs of special interest for EV included skin reactions (15.5%), peripheral neuropathy (6.8%), and hyperglycemia (6.1%). Most common (≥5% ) grade ≥3 treatment-emergent AEs of special interest for P included severe skin reactions (11.8%).

Conclusions

EV+P significantly improved outcomes in pts with previously untreated la/mUC, nearly doubling the median PFS and OS vs chemo. The safety profile was generally manageable with no new safety signals. These results support EV+P as a new SOC for 1L la/mUC.

Clinical trial identification

NCT-04223856.

Editorial acknowledgement

Medical writing and editorial support were provided by Philip Ruane of Envision.

Legal entity responsible for the study

Astellas Pharma, Inc. and Seagen Inc.

Funding

Astellas Pharma, Inc. and Seagen Inc.

Disclosure

T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol Myers Squibb, Ipsen, EUSA Pharma, Merck, MSD, AstraZeneca, AAA; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma, AAA. S. Gupta: Financial Interests, Personal, Advisory Board: Seattle Genetics, BMS, Pfizer, Bayer, Merck, Gilead, Loxo Oncology, Guardant, Foundation one; Financial Interests, Personal, Other, Speaker's Bureau: Janssen; Financial Interests, Personal, Other, Consultant: EMD Serono; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Stocks/Shares: BioNTech, Moderna; Financial Interests, Personal, Steering Committee Member: BMS, Merck, Seattle Genetics, Acrivon; Financial Interests, Institutional, Local PI: EMD Serono, Gilead, Roche, QED, Exelixis, Moderna, Pfizer. E. Kikuchi: Financial Interests, Personal, Invited Speaker: MSD, Bristol, Janssen, Astellas, Merck Biopham, Nippon Kayaku, Pfizer; Financial Interests, Personal, Advisory Board: Astellas, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Takeda, Nippon Kayaku, Kyorin, Taiho, Nippon Shinyaku. J. Hoffman-Censits: Financial Interests, Personal, Other, Consultant: Gilead Sciences, Inc; Financial Interests, Institutional, Research Grant, Providing dug and funding for investigator initiated trial: Genentech; Financial Interests, Institutional, Local PI, Local PI for global Phase III trial: Seagen; Financial Interests, Institutional, Local PI, local PI for national trial: Ikena Oncology; Financial Interests, Institutional, Local PI, Local PI for national trial: Daiichi Sankyo, Inc.; Financial Interests, Institutional, Coordinating PI, Coordinating PI for JAVELIN Medley study: Merck. C. Vulsteke: Financial Interests, Personal, Advisory Board: MSD, Janssen Cilag, GSK, Astellas Pharma, BMS, Leo Pharma, Bayer, AstraZeneca, Pfizer, Merck; Financial Interests, Institutional, Research Grant, Funding for research project on immune related toxicities: MSD. D.E. Castellano Gauna: Financial Interests, Personal, Advisory Board: Pfizer, Roche, BMS, Janssen, Astellas, MSD, Ipsen, AstraZeneca, Novartis, GSK; Financial Interests, Institutional, Local PI: Pfizer, Roche, MSD, BMS, AstraZeneca, Janssen, Astellas, Ipsen, Exelisis, Eisai, Lilly, Bayer, GSK, CLOVIS, QED Therapeutics; Non-Financial Interests, Personal, Other, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation. G. Fornarini: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Bristol Myers Squibb, Janssen, Eisai, Ipsen, Pfizer, Bayer; Financial Interests, Personal, Other, ESMO meeting - travel accomodation: Ipsen. J. Li: Financial Interests, Personal, Invited Speaker: Astellas, Janssen Pharma, Bayer Pharmaceuticals, AstraZeneca, Ono Pharmaceutical, Merck, MSD, Roche, Synmosa, Pfizer, COOK. M. Gumus: Financial Interests, Institutional, Invited Speaker: Pfizer, Gen Pharmaceuticals, Novartis, Bayer; Financial Interests, Institutional, Advisory Board: Amgen, Roche, BMS, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Amgen; Financial Interests, Institutional, Local PI: Jounce Therapeutics. N. Mar: Financial Interests, Personal, Invited Speaker: Eisai, Aveo, Tempus, Seattle Genetics; Financial Interests, Personal and Institutional, Funding, Funding for investigator initiated trial: Gilead. S. Narayanan: Financial Interests, Institutional, Full or part-time Employment: Seagen Inc; Financial Interests, Institutional, Stocks/Shares: Seagen Inc. S. Gorla: Financial Interests, Personal, Other, I have been a full time employee of Astellas since 2012 and part of my role involves review of publications and other documents regarding the clinical trials we have conducted involving our products.: Astellas; Financial Interests, Personal, Full or part-time Employment, I have been a full time employee of Astellas since 2012: Astellas; Non-Financial Interests, Personal, Project Lead, I have been a full time employee of Astellas since 2012 and have a leadership role in the projects that I lead.: Astellas; Non-Financial Interests, Personal, Proprietary Information, I have been a full time employee of Astellas since 2012 and therefore have access to company confidential information about our products.: Astellas. M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Seagen, Pfizer; Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS, Roche, AstraZeneca, 4SC; Financial Interests, Institutional, Steering Committee Member, Local PI + SSC member: BMS, AstraZeneca, MSD, Seagen; Financial Interests, Institutional, Steering Committee Member, Local PI + study co-PI: Janssen; Financial Interests, Institutional, Local PI: GSK. All other authors have declared no conflicts of interest.