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Treatment De-Escalation Shows Promise in Testicular Cancer

— Early trial misses primary PFS endpoint, but "favorable" outcomes seen nonetheless

MedpageToday
Seminoma histology image.

A reduced dose of chemotherapy and involved node radiotherapy (INRT) may be viable for patients with stage IIA or IIB seminoma of the testis, results from a phase II study suggested.

In a group of 116 patients, a single-dose of carboplatin along with de-escalated INRT yielded a 3-year progression-free survival (PFS) rate of 93.7% (90% CI 88.5-96.6), reported Alexandros Papachristofilou, MD, of University Hospital Basel in Switzerland, and colleagues.

While this outcome failed to meet the study's target PFS of 95%, the use of de-escalated chemotherapy and radiotherapy still resulted in "favorable 3-year progression-free survival, similar to standard-of-care approaches, with minimal toxic effects," Papachristofilou and colleagues observed in . "This option warrants further study."

Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. The authors noted that while these options are highly effective, they come with the risk of late toxic effects and secondary malignancies. The aim of this study (SAKK 01/10) was to de-escalate treatment in order to avoid those potential toxic effects.

The authors noted that the 4.5-year follow-up was "too short to conclusively evaluate the long-term effects of INRT; however the markedly reduced irradiated volume should decrease the risk of secondary malignancies based on radiobiological models."

In a , Patrizia Giannatempo, MD, and Nicola Nicolai, MD, both of the Foundation IRCCS National Cancer Institute in Milan, observed that "de-escalation strategies in stage IIA and IIB seminoma are a current unmet clinical need and could be implemented in the coming years."

They agreed that the follow-up in this study was too short "to show a potential advantage in reducing treatment sequelae," but suggested that the efficacy of the combination of carboplatin (area under the curve 7 [AUC7]) plus field-involved node radiotherapy "indicates that this treatment could be a valid alternative for some patients."

The single-arm SAKK 01/10 trial included patients with stage IIA or IIB classic seminoma (either at primary diagnosis or at relapse during active surveillance for stage I) who were enrolled at 10 centers of the Swiss Group for Clinical Cancer Research and 10 from the centers of the German Testicular Cancer Study Group.

Treatment included one cycle of carboplatin (AUC7) followed by INRT (30 Gy in 15 fractions for stage IIA disease and 36 Gy in 18 fractions for stage IIB disease).

In addition to the findings described above, Papachristofilou and colleagues found similar 3-year PFS by seminoma stage:

  • Stage IIA: 95.2% (90% CI 85.5-98.5)
  • Stage IIB: 92.6% (90% CI 85.2-96.4)

One patient died because of a second primary cancer 2.5 years after trial inclusion, resulting in a 3-year overall survival of 99.3% (90% CI 95.3-99.8), while seminoma-specific survival was 100% at the time of the analysis.

Best response on imaging was documented as partial or complete response in 98% of patients (90% CI 94-100).

As for safety, acute adverse events (AEs) of any grade that were associated with treatment occurred in 48% of patients, and were mostly low grade. Grade 3/4 treatment-related AEs were mainly chemotherapy-associated cytopenias (7% of patients), and also included neutropenia (4%), thrombocytopenia (3%), and vomiting (1%).

"The acute toxicity profile in our trial differs from standard-of-care radiotherapy and cisplatin-based combination chemotherapy, which commonly lead to substantial acute toxic effects in around 50% of patients," Papachristofilou and co-authors observed. "This favourable finding is attributed to the INRT approach and comparably mild carboplatin monotherapy."

No late treatment-related AEs of any grade or treatment-related deaths were observed during follow-up. Overall, four patients were diagnosed with second primary tumors.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by the Swiss State Secretariat for Education, Research, and Innovation, as well as the Rising Tide Foundation for Clinical Cancer Research.

Papachristofilou has received honoraria from Astellas, Debiopharm, Janssen, Merck Serono, and Sanofi; and travel support from Astellas, AstraZeneca, and Bayer. Several co-authors reported multiple relationships with industry.

The editorialists had no disclosures.

Primary Source

The Lancet Oncology

Papachristofilou A, et al "Single-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial" Lancet Oncol 2022; DOI: 10.1016/S1470-2045(22)00564-2.

Secondary Source

The Lancet Oncology

Giannatempo P, Nicolai N "What is the best way to treat patients with stage IIA or IIB seminoma?" Lancet Oncol 2022; DOI: 10.1016/S1470-2045(22)00625-8.