Olaparib as salvage treatment for advanced germ cell tumors after chemotherapy failure: Results of the open-label, single-arm, IGG-02 phase II trial.

Authors

null

Ugo De Giorgi

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

Ugo De Giorgi , Giuseppe Schepisi , Giorgia Gurioli , Carmela Pisano , Umberto Basso , Cristian Lolli , Elisabetta Petracci , Chiara Casadei , Sabrina Chiara Cecere , Laura Attademo , Alberto Clemente , Valentina Zampiga , Valentina Galla , Ilaria Cangini , Marilena Di Napoli , Linda Valmorri , Sandro Pignata

Organizations

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; National Cancer Institute of Naples, Naples, Italy, Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy, Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione Pascale, IRCCS, Naples, Italy, INT, Naples, Italy, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl-IRCCS, Meldola, Italy, Uro-Gynecological Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, IRCCS, Naples, Italy, Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Naples, Italy

Research Funding

Pharmaceutical/Biotech Company
Astrazeneca

Background: Therapeutic options for patients with advanced germ cell tumors (GCTs) after multiple relapses or resistant disease are limited. Olaparib is an inhibitor of poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. We aimed to evaluate olaparib activity in patients with refractory GCT. Methods: In this proof-of principle open-label, single-arm, phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ cell cancer IGG-02 study (NCT02533765), patient eligibility included failure after high-dose chemotherapy or after at least 2 different cisplatin-based regimens. Measurements of serum tumor markers and computed tomography were carried out at baseline and every 6 weeks of olaparib treatment. The study primary endpoint was the overall response rate, the study planned to recruit initially 18 patients and not continue further recruitment until one or more responses were observed. Results: Between September 2015 and February 2019, 18 patients, median age 39 years (range, 22-61) were enrolled. The number of prior chemotherapy regimens was: 2 for 3 patients (16.7%), 3 for 5 patients (27.8%), >3 for 10 patients (55.6%). Sixteen cases (89.9%) received prior high-dose chemotherapy with support of hematopoietic progenitor cells. Grade 3-4 adverse events were observed in 5 patients (27.7%). There were no partial responses, 5 cases (27.8%) with stable disease (SD) lasting 3, 4, 4, 7 and 7+ months and 13 (72.2%) progressive disease. The 12-week progression-free survival probability was 27.8% [95% confidence interval (CI): 10.1%-48.9%]. The 12-month overall survival probability was 27.8% (95% CI: 10.1%-48.9%). A germline DNA repair profile panel showed only a BRCA1 mutated case associated with a SD lasted 4 months. Conclusions: Olaparib as a single agent has marginal activity in heavily pretreated GCT patients, however, an anecdotic 4-month SD in the only BRCA mutated patient has been reported. Plans for future studies with olaparib are suggested in combination or following salvage chemotherapy in less pretreated and more selected GCT patients. The Study has been conducted with AstraZeneca contribution. Clinical trial information: NCT02533765.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Genitourinary Cancer—Kidney and Bladder

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Germ Cell/Testicular

Clinical Trial Registration Number

NCT02533765

Citation

J Clin Oncol 38: 2020 (suppl; abstr 5058)

DOI

10.1200/JCO.2020.38.15_suppl.5058

Abstract #

5058

Poster Bd #

127

Abstract Disclosures

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