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

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.

Editorial acknowledgement

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.