All times are listed in CEST (Central European Summer Time)
- Laurence Albiges (Villejuif, Cedex, CEDEX, France)
- Brian I. Rini (Nashville, TN, United States of America)
- Christian K. Kollmannsberger (Vancouver, British Columbia, Canada)
LBA28 - STAR: A randomised multi-stage phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation, in the treatment of locally advanced and/or metastatic renal Cancer (RCC)
- Janet E. Brown (Sheffield, Yorkshire, United Kingdom)
Abstract
Background
There is increasing interest in using treatment breaks in oncology, to reduce toxicity without compromising efficacy. STAR was designed to determine if a tyrosine kinase inhibitor drug-free interval strategy (DFIS) was non-inferior to a conventional continuation strategy (CCS) in the first line treatment of advanced RCC. Outcomes were overall survival (OS) and Quality Adjusted Life Years (QALYs).
Methods
STAR is a UK Phase II/III multicentre, randomised controlled trial. Patients were randomised (1:1) to DFIS or CCS. After 24 weeks of sunitinib/pazopanib treatment, DFIS patients took a treatment break, until disease progression, with additional breaks dependent on disease response and patient/clinician choice. Trial strategy continued until intolerance, progression on treatment or death. Both co-primary endpoints (OS and QALYs) must demonstrate pre-defined non-inferiority (NI) (≤7.5% OS; ≤ 10% QALYs) in intention-to-treat (ITT) and per-protocol (PP) analyses for NI to be concluded. An economic evaluation was also conducted.
Results
920 patients were randomised (461 CCS vs 459 DFIS) from 13/01/12 to 12/09/17. 488 (53.0%) patients (240 (52.1%) vs 248 (54.0%)) continued on trial post-week 24. Median treatment break length was 87 days. ITT and PP analyses included 461 vs 458 and 453 vs 418 patients respectively. There was a difference in conclusion in the OS analysis precluding confirmation of NI (HR (95%CI) ITT: 0.97 (0.83, 1.12); PP: 0.94 (0.80, 1.09) NI Margin: 95%CI ≥0.812). However consistent NI conclusions were found for QALYs (Marginal Effect (95% CI) ITT: -0.05 (-0.15, 0.05); PP: 0.04 (-0.14, 0.21) NI Margin: 95%CI ≥-0.156). At two years, DFIS was associated with cost savings (£6,954 per-participant).
Conclusions
Although OS just fell short of overall defined NI using this rigorous approach, probably due to fewer than expected events, QALY NI was demonstrated and a DFIS was seen to be acceptable to patients and clinicians. DFIS also appeared to be highly cost-effective compared to CCS.
Clinical trial identification
EudraCT 2011-001098-16.
Legal entity responsible for the study
University of Leeds.
Funding
UK National Institute for Health Research (NIHR).
Disclosure
C. Ralph: Financial Interests, Personal, Advisory Board, Travel, accommodation, expenses: Bristol, Myers, Squibb; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Viralytics; Financial Interests, Personal, Other, Travel, accommodation, expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, accommodation, expenses: GlaxoSmithKlyne; Financial Interests, Personal, Other, Travel, accommodation, expenses: Ipsen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Jannsen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche. T.B. Powles: Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Pfizer; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: MSD; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Merck; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Serano; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Roche; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Eisai; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Ipsen; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Seattle Genetics; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: Astellas; Financial Interests, Personal and Institutional, Advisory Board, Academic Funding: AstraZeneca. R. Jones: Financial Interests, Personal and Institutional, Other, Research funding, consultancy: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, Research funding, consultancy, speaker: Pfizer. T. Eisen: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Research Support: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Pfizer. V. Goh: Financial Interests, Institutional, Other, Research Agreement: Siemens Healthcare. All other authors have declared no conflicts of interest.
LBA29 - Nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced renal cell carcinoma: A randomized phase II trial (PRISM)
- Naveen S. Vasudev (Leeds, Yorkshire, United Kingdom)
Abstract
Background
Ipilimumab (IPI) plus nivolumab (N) is a standard first-line treatment for patients (pts) with intermediate and poor-risk advanced renal cell carcinoma (aRCC). Grade 3/4 (G3/4) treatment-related adverse events (trAE) are relatively common during the initial combination period. The aim of this randomized phase II trial was to determine whether modified scheduling of IPI, in combination with N, is associated with improved tolerability, whilst maintaining treatment efficacy in line with previous comparative studies with sunitinib.
Methods
Pts with untreated clear cell aRCC were randomized 1:2 to receive 4 doses of IPI 1mg/kg Q3W (conventional IPI) or Q12W (modified IPI), in combination with N (3mg/kg), until disease progression or unacceptable toxicity. The primary endpoint was the proportion of pts with a G3/4 trAE within 12 months of initiating treatment (from those who received at least one dose of therapy (modified intention-to-treat)). Secondary endpoints included progression-free survival (PFS) at 12 months and objective response rate (ORR).
Results
192 pts (69.8% intermediate/poor-risk) received at least one dose of study drug. G3/4 trAE were significantly lower amongst pts receiving modified IPI compared to conventional IPI (32.8% v 53.1%; OR 0.43 [90% CI: 0.25, 0.72]; p=0.0075). Efficacy endpoints are given in the table and were similar between treatment arms and pre-specified IMDC risk subgroups.
Conclusions
Giving IPI 12-weekly, instead of 3-weekly, in combination with N, was associated with a clinically significant reduction in rates of G3/4 trAE. Outcome data suggested there was no clear reduction in ORR or PFS with the modified schedule and is in line with previous comparative studies with sunitinib (Table).
Best Response n (%) mITT population Intermediate/Poor-risk Modified IPI (n=128) Conventional IPI (n=64) Modified IPI (n=90) Conventional IPI (n=44) Complete Response 8 (6.3) 1 (1.6) 6 (6.7) 1 (2.3) Partial Response 50 (39.1) 22 (34.4) 36 (40.0) 17 (38.6) Stable Disease 40 (31.3) 25 (39.1) 23 (25.6) 17 (38.6) Progressive Disease 29 (22.7) 15 (23.4) 24 (26.7) 9 (20.5) Missing 1 (0.8) 1 (1.6) 1 (1.1) 0 (0.0) 46 (37-55) 45 (32-57) 43 (33-53) 46 (31-60)
Clinical trial identification
EudraCT 2017-001476-33.
Legal entity responsible for the study
University of Leeds/Leeds Teaching Hospitals NHS Trust.
Funding
Bristol Myers Squibb.
Disclosure
N.S. Vasudev: Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Invited Speaker: EUSA Pharma; Financial Interests, Personal, Advisory Board: EUSA Pharma; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: 4D Pharma. L. Pickering: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: NIHR. T.S. Waddell: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: EUSA Pharma; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Eisai. K. Fife: Financial Interests, Personal, Advisory Board: BMS. R. Griffiths: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai. A. Sharma: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Eisai. G. Velikova: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Seattle Geneics; Financial Interests, Institutional, Research Grant: Breast Cancer Now; Financial Interests, Institutional, Research Grant: EORTC; Financial Interests, Institutional, Research Grant: Yorkshire Cancer Research; Financial Interests, Institutional, Research Grant: Pfizer Inc; Financial Interests, Institutional, Research Grant: IQVIA. A. Maraveyas: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Leo; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Leo; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Leo. J.E. Brown: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bayer. B. Venugopal: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EUSA pharma; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Institutional, Principal Investigator: Ipsen; Non-Financial Interests, Institutional, Principal Investigator: Calithera; Non-Financial Interests, Institutional, Principal Investigator: Exelixis. P. Patel: Financial Interests, Personal, Invited Speaker: BMS. S. Symeonides: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Ellipses; Financial Interests, Institutional, Advisory Board: EUSA pharma; Financial Interests, Institutional, Advisory Board: Medannex; Financial Interests, Institutional, Advisory Board: Merck Serono; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Vaccitech; Non-Financial Interests, Institutional, Principal Investigator: BioLineRx; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Verastem. P.D. Nathan: Financial Interests, Invited Speaker: Pleas see ESMO DOI. T.B. Powles: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: J&J; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Exelexis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: J&J; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Exelexis; Financial Interests, Institutional, Research Grant: Eisai. All other authors have declared no conflicts of interest.
653O - Pembrolizumab (pembro) vs placebo as adjuvant therapy for patients (pts) with renal cell carcinoma (RCC): Patient-reported outcomes (PRO) in KEYNOTE-564
- Toni K. Choueiri (Boston, United States of America)
Abstract
Background
The randomized, double-blind, phase III KEYNOTE-564 (NCT03142334) study met its primary endpoint of disease-free survival with adjuvant pembro vs placebo following surgery in pts with RCC. We present PRO findings for adjuvant pembro vs placebo in KEYNOTE-564.
Methods
PRO were evaluated in all randomized pts with ≥1 dose study treatment and ≥1 completed assessment for the specific outcome. FKSI-DRS and EORTC QLQ-C30 were administered electronically at cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 days after last dose, and annually thereafter until recurrence or new therapy. Prespecified secondary endpoints included least square (LS) mean change in symptom scores as measured by FKSI-DRS and health-related quality of life as measured by the QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) scales from baseline to week 52. CIs were nominal and descriptive.
Results
As of Dec 14, 2020, no pts remained on treatment and median (range) time from randomization to data cutoff date was 24.1 (14.9-41.5) months. Among 496 pts randomized to pembro and 498 pts to placebo, >90% completed the FSKI-DRS and QLQ-C30 at baseline and >60% completed each instrument at week 52. LS mean change in FKSI-DRS score was −1.12 (95% CI, −1.53-−0.71) with pembro vs −0.45 (95% CI, −0.84-−0.05) with placebo; both were below the threshold of ≥3 for clinically meaningful change in FKSI-DRS. LS mean change in QLQ-C30 GHS/QoL score was −4.25 (95% CI, −6.32-−2.19) with pembro vs −1.68 (95% CI, −3.69-0.32) with placebo. LS mean change in QLQ-C30 PF score was −1.81 (95% CI, −3.19-−0.43) with pembro vs −0.90 (95% CI, −2.23-0.44) with placebo. Mean score change for both arms in both scales was below the clinically meaningful change threshold of ≥10 for QLQ-C30. Health-related QoL and symptom scores were maintained across all evaluated time points.
Conclusions
No clinically meaningful changes from baseline in health-related QoL or symptom scores were observed with adjuvant pembro or placebo. These scores remained stable over time. PRO findings suggested that adjuvant pembro was tolerable from a pt perspective.
Clinical trial identification
NCT03142334.
Editorial acknowledgement
Medical writing assistance was provided by Ina Nikolaeva of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
T.K. Choueiri: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal and Institutional, Research Grant: BMS; Other, Personal, Other, manuscript preparation, travel/lodging: BMS; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal and Institutional, Research Grant: Exelixis; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Exelixis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal and Institutional, Research Grant: Lilly; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Lilly; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Novartis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: GSK; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: Pfizer; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal, Other, manuscript preparation, travel/lodging: EMD Serono; Financial Interests, Personal, Stocks/Shares: Pionyr; Financial Interests, Personal, Stocks/Shares: Tempest; Financial Interests, Institutional, Funding: Dana-Farber Cancer Institute; Non-Financial Interests, Personal, Invited Speaker: NCCN kidney panel; Non-Financial Interests, Personal, Invited Speaker: NCI Steering Committee. P. Tomczak: Financial Interests, Institutional, Funding: MSD. S.H. Park: Financial Interests, Institutional, Funding: MSD. B. Venugopal: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: EUSA Pharma; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Merck Serono. S. Symeonides: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Verastem; Financial Interests, Personal and Institutional, Advisory Role: Bicycle Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: Ellipses; Financial Interests, Personal and Institutional, Advisory Role: Medannex; Financial Interests, Personal and Institutional, Advisory Role: Vaccitech; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: EUSA; Financial Interests, Personal and Institutional, Advisory Board: EUSA; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Merck Serono; Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Non-Financial Interests, Personal, Other, travel: Ipsen. J. Hajek: Financial Interests, Institutional, Funding: MSD. T. Ferguson: Financial Interests, Institutional, Funding: MSD. Y. Chang: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Janssen. J.L. Lee: Financial Interests, Personal, Advisory Board: Pfizer Korea; Financial Interests, Personal, Advisory Board: Ipsen Korea; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Role: Novartis Korea; Financial Interests, Personal, Advisory Board: Astellas Korea; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Stocks/Shares: Myovant Science; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: SeaGen; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. N. Haas: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Aveo; Financial Interests, Personal, Advisory Role: Roche. P. Sawrycki: Financial Interests, Personal, Advisory Role: MSD. N. Sarwar: Financial Interests, Institutional, Funding: MSD. M. Gross-Goupil: Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Other, honoraria, travel: Amgen; Financial Interests, Personal, Other, honoraria, travel: Astellas; Financial Interests, Personal, Other, honoraria, travel: AstraZeneca; Financial Interests, Personal, Other, honoraria, travel: Bayer; Financial Interests, Personal, Other, honoraria, travel: BMS; Financial Interests, Personal, Other, honoraria, travel: Ipsen; Financial Interests, Personal, Other, honoraria, travel: Janssen; Financial Interests, Personal, Other, honoraria, travel: Merck KGaA; Financial Interests, Personal, Other, honoraria, travel: MSD; Financial Interests, Personal, Other, honoraria, travel: Novartis; Financial Interests, Personal, Other, honoraria, travel: Pfizer; Financial Interests, Personal, Other, honoraria, travel: Roche; Financial Interests, Personal, Other, honoraria, travel: Sanofi. A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, honoraria, travel/lodging: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, honoraria, travel/lodging: AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, honoraria: Sanofi; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Other, honoraria, travel/lodging: Janssen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Other, honoraria, travel/lodging: Ipsen; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other, honoraria: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, honoraria, travel/lodging: MSD; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Other, honoraria, travel/lodging: Roche/Genentech; Financial Interests, Personal, Other, honoraria, travel/lodging: Astellas Pharma. M. Mahave: Financial Interests, Institutional, Funding: MSD. T.L. Saretsky: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. P. Zhang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. J. Willemann-Rogerio: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. D.I. Quinn: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Other, data safety: Eisai; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Bayer. T.B. Powles: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Eisai.
Invited Discussant LBA28, LBA29 and 653O
- Brian I. Rini (Nashville, TN, United States of America)
Q&A and live discussion
- Laurence Albiges (Villejuif, Cedex, CEDEX, France)
LBA30 - Single-dose carboplatin followed by involved-node radiotherapy as curative treatment for seminoma stage IIA/B: Efficacy results from the international multicenter phase II trial SAKK 01/10
- Alexandros Papachristofilou (Basel, Switzerland)
Abstract
Background
Standard treatment options for patients (pts) with seminoma clinical stage (CS) IIA/B are either extensive “dog-leg” para-aortic/pelvic radiotherapy (RT) or 3-4 cycles of cisplatin-based combination chemotherapy (ChT) with a 3-year progression free survival (PFS) of ≥90%, but potential acute and late toxicities. SAKK 01/10 is a trial of the Swiss Group for Clinical Cancer Research (SAKK) and the German Testicular Cancer Study Group (GTCSG) aiming at reducing therapy toxicity while preserving efficacy in CS IIA/B seminoma by combining deescalated ChT and RT. We previously reported very low acute toxicity (ASCO GU 2020).
Methods
SAKK 01/10 is a multicenter, single arm, phase II study in pts with CS IIA/B seminoma (de novo or relapse on active surveillance). Treatment consisted of 1 cycle carboplatin AUC7 followed by involved-node RT (IIA: 30 Gy; IIB: 36 Gy). The primary endpoint is 3-year PFS. With a target 3-year PFS of 95%, 120 patients were required to show that the lower limit of a two-sided 90% confidence interval is >90%. Secondary endpoints include time to progression (TTP), overall survival, patterns of tumor progression, acute and chronic adverse events, including secondary malignancies.
Results
A total of 120 pts were included from 10/2012 until 06/2018 in 20 centers in Switzerland and Germany. 116 pts were eligible and started treatment per protocol (IIA: 46, IIB: 70; de-novo: 76, relapsing: 40). Median age was 40 years (range 22-68). Minimal follow up from inclusion of last patient is 3 years, median follow-up time is 4.5 years (range: 0.8 years - 8.1 years). The 3-year PFS is 93.7% (90% CI [88.5%, 96.6%]), IIA: 95.2% (90% CI [85.5%, 98.5%]), IIB: 92.6% (90% CI [85.1%, 96.4%]). In total, 7 patients developed a recurrence (1 CS IIA, 6 CS IIB), all outside the RT volumes and all salvaged with conventional ChT.
Conclusions
SAKK 01/10 is the largest completed prospective trial in seminoma stage IIA/B to date. A favorable 3-year PFS using the combination of single dose carboplatin AUC7 and involved node RT was achieved. At the same time, adverse event rates were very low. Based on our data, this treatment regimen can be viewed as an attractive option in CS IIA/B seminoma.
Clinical trial identification
NCT01593241.
Legal entity responsible for the study
Swiss Group for Clinical Cancer Research (SAKK).
Funding
State Secretariat for Education, Research and Innovation (SERI) Swiss Cancer Research Foundation (SCS) Swiss Cancer League (SCL) Rising Tide Foundation for Clinical Cancer Research (RTFCCR).
Disclosure
A. Papachristofilou: Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: Merck; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Astellas; Financial Interests, Personal and Institutional, Invited Speaker, Travel Expenses: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, Travel Expenses: Bayer. P. Putora: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Takeda. D. Zihler: Financial Interests, Personal and Institutional, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Pierre-Fabre; Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Advisory Board: Merck; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Advisory Board: Sanofi. S. Gillessen: Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Personal and Institutional, Funding: RSI; Financial Interests, Personal and Institutional, Advisory Role: AAA International; Financial Interests, Personal and Institutional, Advisory Role: Amgen; Financial Interests, Personal and Institutional, Advisory Role: Aranda; Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Bayer; Financial Interests, Personal and Institutional, Advisory Role: BMS; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: Menarini Silicon Biosystems; Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: Orion Pharma; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: Sanofi; Financial Interests, Personal and Institutional, Advisory Role: Telixpharma; Financial Interests, Personal and Institutional, Advisory Role: Tolero; Financial Interests, Personal and Institutional, Funding: ProteoMedix. R. Cathomas: Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Advisory Board: Astellas; Financial Interests, Personal and Institutional, Advisory Board: Janssen; Financial Interests, Personal and Institutional, Advisory Board: Ipsen; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Personal and Institutional, Funding: Astellas; Financial Interests, Personal and Institutional, Funding: BMS; Financial Interests, Personal and Institutional, Funding: MSD; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Personal and Institutional, Funding: AstraZeneca. All other authors have declared no conflicts of interest.
Invited Discussant LBA30
- Christian K. Kollmannsberger (Vancouver, British Columbia, Canada)
Q&A and live discussion
- Laurence Albiges (Villejuif, Cedex, CEDEX, France)