Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease

Author(s): Jack P. Gleeson, MB BCh BAO, MRCPI^1,2; Andrea Knezevic, MS³; Maria Bromberg, MPH⁴; Sujata Patil, MD³; Brett S. Carver, MD^5,6; Manjit Bains, MD^5,6; David R. Jones, MD^5,6; Joel Sheinfeld, MD^5,6; Dean F. Bajorin, MD^4,6; George J. Bosl, MD^4,6; Deaglan J. McHugh, MD^4,6; Samuel A. Funt, MD^4,6; Robert J. Motzer, MD^4,6; Darren R. Feldman, MD^4,6

Source: https://doi.org/10.1200/JCO.23.0254

Dr. Anjan Patel's Thoughts

TIP will likely become the established salvage therapy for GCT’s if this study’s findings are confirmed in the ongoing Phase III TIGER trial.

PURPOSE

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP.

PATIENTS AND METHODS

Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score.

RESULTS

Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively.

CONCLUSION

TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

Author Affiliations

¹Cancer Research @UCC, College of Medicine and Health, University College Cork, Cork, Ireland; ²Medical Oncology Department, Cork University Hospital, Cork, Ireland; ³Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; ⁴Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; ⁵Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY; ⁶Weill Cornell Medical College, New York, NY

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