PFS boost with atezolizumab–chemotherapy in advanced urothelial carcinoma
medwireNews: Adding atezolizumab to chemotherapy significantly prolongs progression-free survival (PFS) in the first-line advanced urothelial cancer setting, according to the IMvigor130 trial results presented at the ESMO Congress 2019.
This phase III trial is “the first immune checkpoint inhibitor study to demonstrate an improvement in PFS over standard of care” in this patient population, presenting author Enrique Grande (MD Anderson Cancer Center Madrid, Spain) told delegates in Barcelona, Spain.
IMvigor130 accrued 1213 individuals with locally advanced or metastatic disease regardless of whether they were eligible for cisplatin-based chemotherapy or not. Participants were randomly assigned to receive atezolizumab 1200 mg every 3 weeks, either alongside physician’s choice of platinum-based chemotherapy and gemcitabine, or as a single-agent, or to receive placebo plus chemotherapy.
Over a median follow-up of 11.8 months, the co-primary endpoint of PFS was significantly longer with the addition of atezolizumab rather than placebo to chemotherapy, at a median of 8.2 versus 6.3 months, and hazard ratio (HR) for progression or death of 0.82.
Enrique Grande tells us why the IMvigor130 data, although very promising, are not quite ready for translation to the clinic yet (1:43):
An interim analysis for the comparison of overall survival (OS) between these two treatment arms – also a primary endpoint – showed a promising trend favoring the atezolizumab combination, at a median of 16.0 months compared with 13.4 months for chemotherapy alone (HR=0.83), but the p-value “did not cross the prespecified interim efficacy boundary,” and follow-up will continue, said Grande.
The investigators also performed an interim analysis for the third co-primary endpoint – OS in the atezolizumab monotherapy versus chemotherapy alone group. There was no OS gain with atezolizumab in the overall population (HR=1.02), but in the subgroup with high PD-L1 levels (IC2/3), the immune checkpoint inhibitor was associated with longer median OS than chemotherapy alone, at unreached versus 17.8 months (HR=0.68), albeit without reaching statistical significance at this stage.
By contrast, the median OS durations were comparable between atezolizumab- and chemotherapy-treated patients with low PD-L1 levels (IC0/1), at 13.5 and 12.9 months, respectively.
With regard to safety, Grande noted that “no unexpected adverse events were observed,” and “the toxicity was consistent with the toxicity profile of the individual agents used.”
The proportion of patients who discontinued due to toxicity was identical for the atezolizumab plus chemotherapy and placebo plus chemotherapy groups, at 34%. Of note, the discontinuation rate was much lower in the atezolizumab monotherapy arm, at 6%.
“The results from IMvigor130 support atezolizumab plus chemotherapy as an important new treatment option for patients with untreated metastatic urothelial carcinoma,” concluded Grande.
Thomas Powles (Barts Cancer Institute, London, UK), who discussed these findings at the session, commented that the atezolizumab–combination data are “statistically significant but not clinically transformative without OS,” while the data for the monotherapy arm are “clinically meaningful but not statistically robust enough yet.”
He believes, however, that IMvigor130 and other trials, such as those investigating enfortumab vedotin plus pembrolizumab and other combinations, “are going to change bladder cancer forever in the near future.”
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