732P - Efficacy and safety of high-dose chemotherapy as second or subsequent salvage therapy in relapsed or refractory germ cell cancer patients: A multicentric analysis

Background

Recurrent metastatic germ cell cancer (GCC) is treated with salvage chemotherapy (CTX), either with high-dose (HD) CTX such as carboplatin and etoposide (HD-CE) or conventional-dose cisplatin-based chemotherapy (CD CTX). For relapse after first salvage CD CTX, HD-CTX is still a curative option, but data on efficacy and safety of HD-CTX in this setting is limited. This retrospective study aimed to explore the efficacy and safety of HD-CTX used as either first or subsequent salvage treatment.

Methods

Data on patients (pts.) characteristics, treatment outcome and safety were retrospectively collected from international expert centres to compare between Group A (HD-CTX as first salvage therapy) and Group B (HD-CTX at recurrence after or progression during salvage CD CTX). Analysis was conducted using R with Wilcoxon, χ² and log-rank test to compare characteristics and survival.

Results

A total of 275 GCC pts. from 18 centers were included in this analysis, 159 pts. (57.8%) in group A and 116 patients (42.2%) in group B. Treatment was conducted with HD-CE in 238 pts. (86%), with a median follow-up time from first salvage CTX of 27 months (SD 51.9) in group A and 35 months (SD 58.7) in group B. Patient characteristics including primary histology, IGCCCG risk, IPFSG score and locations of metastases were equally distributed in both groups. The median OS from first salvage treatment initiation was not reached (group A) versus 68.8 months (group B) (p=0.073), and from HD-CTX treatment not reached (group A) versus 31.2 months (group B) (p=0.002). The 2- and 5-year OS rates after HD-CTX were 76%/65% for group A and 56%/42% for group B, respectively. The objective response rate following HD-CTX was 79% (group A) versus 60% (group B) (p=0.013). Regarding toxicity, adverse events (other than hematologic) were reported in 59% in group A and 73% in group B (p=0.028). Treatment associated deaths were described in 8 patients (2.9%) with no difference between group A versus group B (p=0.221).

Conclusions

Salvage HD-CTX has curative potential in relapsed and refractory GCC patients leading to 65 % long-term survival when used as first salvage therapy and approximately 41% when used in the subsequent salvage setting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, EISAI, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. A.J. Weickhardt: Financial Interests, Personal, Advisory Board: Merck, Ipsen, Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Coordinating PI, PCR MIB funding: Merck. P. Grimison: Financial Interests, Institutional, Local PI, GS-2475: Gilead; Financial Interests, Institutional, Local PI, INCSHR01210: Tigermed; Financial Interests, Institutional, Local PI: Pfizer, Boston Biomedical, Medimmune, Halozyme, Aslan Pharmaceuticals, Janssen, Prime Therapeutics, Epizyme, Plexxikon, Five Prime Therapeutics, Novartis, QED; Financial Interests, Institutional, Local PI, Pembrolizmab: Merck; Financial Interests, Institutional, Local PI, Local PI on commercial trial: PTC Therapeutics; Non-Financial Interests, Project Lead, P3 accelerated BEP clinical trial: Australian and New Zealand Urogenital and Prostate cancer trials group (ANZUP)-non-commercial academic collaborative group; Non-Financial Interests, Leadership Role, TIGER clinical trial-Australia/New Zealand national lead investigator: Australian and New Zealand Urogenital and Prostate cancer trials group (ANZUP)-non-commercial academic collaborative group; Non-Financial Interests, Project Lead, Study chair for government-funded randomised trial of medicinal cannabis with free drug supply by Tilray: NHMRC Clinical Trials Centre, University of Sydney; Other, Member-role in decisions regarding reimbursement of drugs: Australian Government-Pharmaceutical Benefits Advisory Committee; Non-Financial Interests, Leadership Role, Member of scientific advisory committee: Australian and New Zealand Sarcoma Association (ANZSA)-non-commercial academic collaborative group; Non-Financial Interests, Member: Medical Oncology Group of Australia (MOGA). C. Oing: Financial Interests, Personal, Invited Speaker, Renal Cancer Expert Panel Case Presentation: Ipsen; Financial Interests, Personal, Invited Speaker, Talk on Pain Management in GU Cancer Patients: Medac; Financial Interests, Personal, Invited Speaker, Case Presentation Soft Tissue Sarcoma: Roche; Financial Interests, Personal, Advisory Board, Ad Board on discussing novel educational events for young haematologists: Novartis; Financial Interests, Personal, Invited Speaker, Science Slam with a presentation on young professional support from oncological societies in Germany: AstraZeneca; Financial Interests, Personal, Advisory Board, AdBoard assessing educational needs for oncology professionals regarding G-CSF use: Sandoz; Financial Interests, Personal, Invited Speaker, Presentation on Burnout and Resilience in medical oncology professionals: Asklepios Hamburg; Financial Interests, Personal, Advisory Board, Larotrectinib use in sarcoma: Bayer; Financial Interests, Personal, Advisory Board, Experiences with Cabo/Nivo as first-line treatment for metastatic RCC: Ipsen; Non-Financial Interests, Other, Clinical Advisory role in early drug discovery with a fellowship position affiliated with Astex Pharmaceuticals, Cambridge, UK: Astex Pharmaceuticals; Non-Financial Interests, Institutional, Product Samples, Cytotoxic Agent for Preclinical Experiments: PharmaMar. W. Alsdorf: Financial Interests, Personal, Other, Travel Grant: BioNTech; Financial Interests, Personal, Invited Speaker: Janssen. C. Bokemeyer: Financial Interests, Personal, Advisory Board, advisory boards and speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Roche Pharma, AOK Germany; Financial Interests, Personal, Advisory Board: Bayer Healthcare, AstraZeneca, Oncology Drug Consult CRO, Jansen Cilag, BioNTech; Financial Interests, Personal, Advisory Board, Boards attended and lectures given: Sanofi Aventis; Financial Interests, Personal, Advisory Board, and lectures given: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, orgaistion for medical education: med update; Financial Interests, Institutional, Local PI, our department is involved in several clincal trials sponsored by industry and cooperative groups where we hold praticipants roles and local PI roles and PI roles: more than 95 clinical trials; Non-Financial Interests, Member of Board of Directors: DGHO, Northern German Society of Internal Medicine; Non-Financial Interests, Leadership Role: Hamburg Cancer Society, National Network of German Cancer Centers (DKH); Non-Financial Interests, Advisory Role, Board of DGHO Advisors: DGHO. B. Tran: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Astellas, Bayer, BMS, Ipsen, IQVIA, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Tolmar, Sanofi Ammunix; Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayer, BMS, Merck, Pfizer; Financial Interests, Institutional, Research Grant: Amgen, Astellas, AstraZeneca, Bayer, BMS, Genentech, Ipsen, Janssen, Pfizer, MSD; Financial Interests, Personal, Steering Committee Member: CG Oncology, Janssen, MSD. All other authors have declared no conflicts of interest.