Triplet chemotherapy may benefit intermediate-, poor-risk germ cell tumors

A chemotherapeutic triplet comprised of paclitaxel, ifosfamide and cisplatin exhibited efficacy as first-line treatment for patients with intermediate- or poor-risk germ cell tumors, according to the results of a prospective phase 2 study.

“Germ cell tumors are considered a model of curable cancer, given their exquisite sensitivity to cisplatin-based chemotherapy, which allows durable complete responses to be achieved, even in the face of widely metastatic disease,” Darren R. Feldman, MD, urologic oncologist at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “However, the likelihood of sensitivity to chemotherapy and cure varies significantly on the basis of clinical and pathologic factors, which have been incorporated into the International Germ Cell Cancer Collaborative Group prognostic model.”

Good-risk patients have a 90% PFS rate after chemotherapy under this model, whereas the PFS rate is 70% to 75% for intermediate-risk patients and 45% to 55% for poor-risk patients.

Randomized trials have shown suboptimal OS for intermediate- and poor-risk patients treated with etoposide and cisplatin, with or without bleomycin, the current standard of care.

Feldman and colleagues sought to evaluate the efficacy of paclitaxel, ifosfamide and cisplatin as a first-line therapy in this patient population.

The researchers conducted a multicenter trial that included data from 60 previously untreated patients (median age, 28 years; range, 18-56; 98% men), whom they assigned to four treatment cycles.

The majority of patients (n = 40) had poor-risk tumors; the remaining 20 patients had intermediate-risk tumors.

Treatment cycles consisted of 240 mg/m² of paclitaxel, given over 2 days; 6 g/m² of ifosfamide, given over 5 days with mesna support; and 100 mg/m² of cisplatin, given over 5 days. Treatment occurred once every 3 weeks, and patients received granulocyte colony–stimulating factor as a support medication.

Complete response served as the primary endpoint.

Sixty-eight percent (n = 28) of the first 41 evaluable patients achieved a complete response, meeting the study’s primary endpoint.

Among all evaluable patients (n = 56), 68% (n = 38) achieved a complete response. An additional 13% (n = 7) achieved partial responses with negative markers, for a favorable response rate of 80% (95% CI, 68-98).

The favorable response rates by subtype were 94% (95% CI, 73-100) for intermediate-risk patients and 74% (95% CI, 57-87) for poor-risk patients.

Thirty-eight patients underwent surgery after chemotherapy to resect residual masses; however, a majority of patients with negative markers (n = 5) could not receive surgery due to seminoma.

All patients were evaluable for PFS and OS, with a median follow-up of 4.4 years (range, 1-7.6). The entire cohort had a 3-year PFS estimate of 72% (95% CI, 61-84), with six relapses recorded (poor risk, n = 5; intermediate risk, n = 1).

The researchers observed a significant difference in PFS between intermediate-risk (90%; 95% CI, 78-100) and poor-risk (63%; 95% CI, 49-80) patients (P = .035).

The 3-year OS rate for all patients was 91% (95% CI, 84-99). All intermediate-risk patients remained alive. Five patients with poor-risk tumors died, two of whom developed a secondary somatic malignancy (spindle cell sarcoma and acute myeloid leukemia) that contributed to progression and death.

Eleven patients developed neutropenic fever and six patients had paclitaxel hypersensitivity reactions. No patients died due to treatment.

“Comparison with bleomycin, etoposide and cisplatin in a randomized trial is necessary before paclitaxel, ifosfamide and cisplatin can be established as a standard-of-care option for patients with newly-diagnosed intermediate- or poor-risk germ cell tumors,” Feldman and colleagues wrote. “Nevertheless, the favorable results achieved here support conduct of such a study, and a randomized phase 2 trial ... has therefore been initiated in this population.” – by Cameron Kelsall

Disclosure: Feldman reports research funding from Novartis, consultant roles with Bayer and Seattle Genetics, and that an immediate family member holds a consultant role with Gilead Sciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.