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

Association Between Systemic Anticancer Therapy Administration Near the End of Life With Health Care and Hospice Utilization in Older Adults: A SEER Medicare Analysis of End-of-Life Care Quality

Maybe I’m biased as chair of the VBC, but this study showed that all subtypes of SACT use were associated with markers of poorer-quality EOL care.

Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline

Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.

Novel Systemic Anticancer Treatments and Health Services Use the End of Life Among Adults With Cancer

This study reviewed the effects of using novel agents (immunotherapy and targeted therapy) in patients at the end of life (EOL), based on the perception that these therapies may be less toxic than chemotherapy. Adjusted odds of high health service utilization and hospital death were more than twofold greater among patients receiving systemic anticancer therapy (SACT) at the EOL compared to those receiving none.

Prescribing Changes After Accelerated vs Regular Approval of Oncology Therapies

This study analyzed prescribing patterns for oncology drugs granted FDA Accelerated Approval (AA) versus those later converted to Regular Approval (RA) using data from over 63,000 patients with advanced solid tumors. Prescribing of AA drugs increased sharply—by an average of 23 percentage points—immediately after AA, while conversion to RA led to only a minimal further increase. Off-label use of AA drugs, either in earlier lines of therapy or in biomarker-negative patients, was rare. The findings suggest that oncologists rapidly adopt AA drugs into practice, often without waiting for confirmatory evidence required for RA. In summary, AA status drives substantial and immediate uptake of oncology drugs, highlighting the importance of timely confirmatory trials to ensure clinical benefit.

Mapping the rapid growth of multi-omics in tumor immunotherapy: Bibliometric evidence of technology convergence and paradigm shifts

The article demonstrates that multi-omics research in tumor immunotherapy has grown rapidly since 2019, with China leading in publication volume but showing limited international collaboration. Early research focused on immune checkpoint blockade, while recent trends emphasize machine learning, multi-omics integration, and lncRNA, reflecting a shift toward predictive modeling and biomarker discovery. Multi-omics approaches have enabled the development of immune infiltration-based prognostic models and identified metabolic and spatial biomarkers, such as oxidative phosphorylation in melanoma and ENPP1 in Ewing sarcoma, which may guide therapeutic strategies. Overall, the study provides a systematic framework for tracking technological convergence and emerging frontiers, highlighting the need for longitudinal omics monitoring, AI-driven integration, and enhanced international collaboration to optimize precision-driven tumor immunotherapy.