medwireNews: Phase 2 trial investigators say that short-term upfront treatment with the immune checkpoint inhibitor avelumab followed by the combination of avelumab and carboplatin–gemcitabine is not an appropriate strategy for treatment-naïve, cisplatin-ineligible patients with metastatic urothelial carcinoma (UC).
Presenting the findings at the ESMO Virtual Congress 2020, Begoña Perez Valderrama (Hospital Universitario Virgen del Rocio, Sevilla, Spain) explained that “retrospective studies have observed a high response rate with chemotherapy after immunotherapy in a [chemotherapy]-naïve population,” pointing to a role for induction immunotherapy.
“We [therefore] hypothesized that avelumab given pre-emptively and in an alternate or sequential way with [carboplatin–gemcitabine] will result in antitumor activity that is significantly superior to standard chemotherapy,” she told delegates.
The INDUCOMAIN trial included 85 cisplatin-ineligible patients with untreated unresectable or metastatic UC who were randomly assigned to receive two cycles of induction therapy with avelumab 10 mg/kg every 2 weeks, followed by six cycles of avelumab 10 mg/kg every 3 weeks plus standard doses of carboplatin–gemcitabine, and subsequent maintenance with avelumab 10 mg/kg every 2 weeks, or to receive six cycles of standard carboplatin–gemcitabine alone.
Perez Valderrama reported that the primary endpoint of overall response rate (ORR) was 57.1% in the avelumab group and 53.5% in the chemotherapy alone group after a median follow-up of 12.4 and 15.1 months, respectively.
She noted that although the ORR in the avelumab arm exceeded the prespecified rate of 45%, the “unexpectedly” higher rate observed in the control arm meant that the superiority of the avelumab-based regimen to standard chemotherapy could not be established.
There was also no significant difference between the avelumab and control groups with regard to median progression-free survival (6.9 vs 7.4 months) or overall survival (OS; 10.5 vs 13.2 months). However, the OS rate at 15 months was numerically higher with avelumab than chemotherapy alone, at 51.28% versus 38.96%.
Of note, nearly a third (31.0%) of avelumab-treated patients progressed or died before or at the first planned assessment for response, compared with 9.3% of those given chemotherapy alone, despite no imbalances between the groups in terms of adverse prognostic factors.
The presenter therefore concluded that “induction immunotherapy alone before [chemotherapy]–immunotherapy is not an appropriate strategy,” and “the previous hypothesis that immunotherapy before [chemotherapy] might optimize subsequent chemotherapy response was not proven.”
She added: “Ongoing phase 3 trials that will be presented soon are looking at different sequencing or combination approaches.”
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany