The regimen has demonstrated significantly superior efficacy and tolerability to chemotherapy.
Combining an antibody-drug conjugate (ADC) monotherapy with a PD-1 inhibitor has outperformed chemotherapy in a new phase three trial.
Disitamab vedotin plus toripalimab was superior to chemotherapy (gemcitabine plus cisplatin or carboplatin) in progression-free survival (13.1 months vs 6.5 months), overall survival (31.5 months vs 16.9 months) and objective response rate (76.1% vs 50%).
The dual therapy was also better tolerated than chemotherapy; grade three or higher treatment-related adverse events occurred in 55% of patients, compared with 87% in the chemotherapy group.
The median duration of response to the ADC-immunotherapy was 14.6 months compared to 5.6 months in the chemotherapy group.
Dr Harriet Herbison, medical oncologist at Monash Health, said it was a well conducted study with a fantastic result.
“While the number of patients recruited to the study are modest for a phase III study, there is no doubt in the trial results given an almost a doubling in overall survival which is incredibly meaningful to patients” she told Oncology Republic.
The multicentre, open-label, randomised trial included nearly 500 adults with unresectable and untreated HER2-expressing locally advanced or metastatic urothelial cancer.
In a 1:1 ratio, participants received either disitamab vedotin plus toripalimab every two weeks or chemotherapy every three weeks. Disitamab vedotin was given at a dose of 2mg per kg of body weight and toripalimab at a dose of 3mg per kg.
“What is also significant about this study is it offers a personalised therapy option to patients as only HER2 1-3+ IHC patients were included,” Dr Herbison said.
Patients in the chemotherapy group received standard-dose cisplatin or carboplatin on day one with gemcitabine on days one and eight.
The chemotherapy group had a maximum number of six treatment cycles, while the disitamab vedotin plus toripalimab group had no set maximum number of cycles. This reflected superior tolerability of the treatment, Dr Herbison explained.
The median number of cycles in the ADC-immunotherapy group was 14, with treatment ranging from two to 144 weeks.
The median follow-up was 18 months, median age was 66 years, around 70% were male and more than three quarters had a HER2 IHC score of 2+ or 3+.
Adverse events which led to treatment discontinuation of occurred in 12.3% of the patients receiving disitamab vedotin plus toripalimab and in 10.4% of the chemotherapy group.
The tumour origin for roughly half of the cohort was the upper urinary tract. The trial was conducted across 72 sites in China.
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Of the 121 chemotherapy patients who experienced an objective response, three were a complete response.
In the disitamab vedotin plus toripalimab group, 11 of the 185 patients had a complete response.
The FDA granted disitamab vedotin, the ADC monotherapy, a “breakthrough therapy” designation for treating HER2-positive locally.
It is an established treatment following chemotherapy and is approved in the US and China, but is not yet approved in Australia.
Dr Herbison highlighted an ongoing phase III randomised controlled trial comparing disitimab vedotin plus pembrolizumab, another PD-1 inhibitor, to chemotherapy.
“This is an international multi-centre study … and will add to the evidence and likely the confidence in the results of this combination.”
