The University of Texas MD Anderson Cancer Center, Houston, TX
Yago Nieto , Shi-Ming Tu , Matthew T. Campbell , Roland Bassett , Nizar M. Tannir , John Francis Ward , Wayne Lewis Hofstetter , Roy B. Jones , Borje Andersson , Alison M Gulbis , Celina Ledesma , Melissa Timmons , Michelle Trapp , Richard E. Champlin , Lance C. Pagliaro
Background: Tandem HDC with carbo/etoposide (CE) is curative for a portion of relapsed GCT pts. However, outcomes of refractory or high-risk relapsed pts remain poor. We tested a new HDC regimen of GemDMC, based on DNA damage repair inhibition. We combined BEV with HDC given their potential synergy and the high vascularity of GCT metastases. Methods: Eligibility: Intermediate (int)/high-risk (Beyer Model), creatinine ≤1.8 mg/dL and adequate organ function. HDC included BEV (5 mg/kg) preceding GemDMC (HDC #1) and ifosfamide/CE (ICE) (HDC #2). Following accrual of 42 pts, we amended the trial omitting BEV. The trial was powered to distinguish a target 50% 2-yr RFS from an expected 25% in this population. Results: We enrolled 69 male pts in cohorts 1 (BEV, N=42) and 2 (no BEV, N=27) (Table). Pts were heavily pretreated and most had refractory tumors. Main AE: mucositis and renal (4 HDC-related deaths in cohort 1, 1 in cohort 2). Tumor markers normalized in 90% pts with active tumors at HDC. After HDC, 19 pts were in CR and 28 in PRm- (of these, 22 had residual lesions resected with no viable tumor found in 20/22, 2 xRT, 4 monitored). Median f/u = 39 (2-105) mo. The 2-yr RFS rates in cohorts 1 and 2 = 52% and 78%, respectively. Their respective 2-yr OS rates = 55% and 81%. Conclusions: Sequential HDC with GemDMC–ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the anticipated results. Addition of BEV increases toxicity but not tumor control. Clinical trial information: NCT00936936
BEV (N=42) | No BEV (N=27) | P | |
---|---|---|---|
Median age (range) | 30 (20 - 49) | 28 (19-56) | .9 |
1◦ testis / mediast / retroperit (%) | 76 / 14 / 10 | 85 / 11 / 4 | .7 |
Median # prior regimens | 4 (2 - 9) | 4 (2-8) | .7 |
Tumor markers at rel/PD: median (range) | |||
AFP (N=29) | 395 (25–377,426) | 1,942 (17-750,303) | .4 |
B-HCG (N=34) | 344 (26–89,000) | 1,482 (22-24,579) | .5 |
Prior progression-free interval (%) | |||
≤3 mo | 90 | 89 | .9 |
>3 mo | 10 | 11 | |
# prior rel/PD (%) | |||
1 | 24 | 37 | .2 |
2 | 18 | 30 | |
3-6 | 58 | 33 | |
Cisplatin sensitive (%): | |||
Absol refr | 39 | 29 | .2 |
Refr | 45 | 39 | |
Sensit | 16 | 32 | |
% prior surgery of mets | 60 | 67 | .6 |
% prior xRT | 21 | 30 | .6 |
Resp at HDC #1 (%): | |||
No resp (PD / SD) | 58 (53 / 5) | 32 (26 / 6) | .02 |
PRm+ | 18 | 55 | |
PRm- | 13 | 10 | |
CR | 11 | 3 | |
Risk (%): | |||
Beyer: Int / high | 48 / 52 | 62 / 38 | .3 |
IPS: Int / high / very high | 5 / 14 / 81 | 7 / 22 / 70 | .9 |
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Abstract Disclosures
2014 ASCO Annual Meeting
First Author: Yago Nieto
2012 ASCO Annual Meeting
First Author: Yago Nieto
2022 ASCO Genitourinary Cancers Symposium
First Author: Jennifer King
2024 ASCO Genitourinary Cancers Symposium
First Author: Federico Losco