707P - Paclitaxel, ifosfamide and cisplatin (TIP) in patients (pts) with poor prognosis nonseminomatous germ cell tumor (NSGCT) with unfavourable serum tumor markers (STM) decline: A phase II study

Background

More than 30% of pts with poor prognosis NSGCT will relapse after standard frontline chemotherapy. Unfavourable STM decline may be an early predictor of treatment failure (K.Fizazi, 2014). We aimed to evaluate efficacy of therapy intensification with TIP regimen in this subset of pts.

Methods

This was phase II multicenter prospective trial. We enrolled pts ≥18 years with advanced poor prognosis per original IGCCCG risk groups. All pts received 1 cycle of BEP regimen with tumor markers kinetics assessment on 18-21 d of cycle. Pts with unfavorable STM decline received four cycles of TIP regimen (paclitaxel 120 mg/m2 d 1–2, ifosfamide 1500 mg/m2 d 2–5 (+mesna), and cisplatin 25 mg/m2 d 2–5 with G-CSF support) with subsequent surgical treatment for pts with resectable disease ≥1 cm. The primary endpoint was 1-year progression-free survival (PFS) (48 pts should be included to detect a 20% difference in 1-year PFS (H0 – 55%, H1 – 75%) with two-sided alpha 5% and a power of 80%).

Results

Between 2017 and 2023, 34 pts were enrolled (primary mediastinal – 6 (18%), non-pulmonary visceral metastasis – 19 (56%), 10 (30%) – dose-reduced 1^st cycle due to high risks (ECOG 3-4, ultra-high levels of STM)). With median follow-up 21.6 months (4.6–64.9 months) 12 PFS events were observed, local monitoring committee recommended to analyze data preliminary. The 1-year PFS and overall survival were 55% (39–72) and 76% (62–91), respectively. The favorable response rate (complete response (CR) + partial response with negative STM) was achieved in 20 (59.4%) pts. Sixteen (47%) pts underwent surgery following chemotherapy. Pathological CR was achieved in 9 (26%) pts, mature teratoma and viable tumor were observed in 5 (15%) pts in each group postoperatively. Myelosuppression was the main toxicity; febrile neutropenia was observed in 15 (44%) pts.

Conclusions

Compared to historical data the TIP regimen did not improve outcomes of pts with unfavorable decline STM after the first cycle of chemotherapy. Further trials are needed to assess the optimal approach for this subgroup of pts.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ministry of Health of the Russian Federation.

Disclosure

All authors have declared no conflicts of interest.