Dr. Enrique Grande presents the final progression-free survival analysis of IMvigor130 as well as an interim analysis of overall survival. IMvigor130 is a 3-arm randomized placebo-controlled trial of platinum-based chemotherapy alone versus platinum chemotherapy plus atezolizumab versus atezolizumab alone for the treatment of patients with metastatic urothelial carcinoma in the first-line setting. The co-primary endpoints were progression-free and overall survival, and the precise chemotherapy regimen (cisplatin versus carboplatin) was deferred to the clinical judgments of the treating investigators.
A total of 1213 patients were randomized. All 3 arms were generally well-balanced with respect to age (median 67-69) and PD-L1 status. However, it is noteworthy that a preponderance of patients in the combination atezolizumab plus platinum arm were deemed cisplatin-ineligible per Galsky criteria and a slightly higher proportion of these patients went on to receive carboplatin (70%) relative the platinum chemotherapy plus placebo arm (66%).
The study met its primary endpoint, with atezolizumab plus platinum chemotherapy achieving a statistically significant improvement in progression-free survival (hazard ratio 0.82, p(one-sided) = 0.007). The chemo-immunotherapy combination was associated with a 1.9-month improvement (8.2 months versus 6.3 months) in median progression-free survival.
Subgroup analyses generally favored atezolizumab plus platinum-based chemotherapy. Interestingly, the IC2/3 (PD-L1-high) subgroup and the subgroup treated with cisplatin both exhibited a statistically significant improvement in progression-free survival in favor of the combination.
In terms of overall survival, while there was a trend toward improved survival with the combination, this result did not reach statistical significance (HR 0.88 95%CI [0.69 – 1.00]). Nevertheless, atezolizumab plus platinum chemotherapy was associated with a numerically higher median overall survival (16.0 months) compared to platinum chemotherapy plus placebo (13.4 months).
Per protocol, results were stratified according to PD-L1 status. While no significant difference was observed with respect to overall survival among PD-L1-low patients, there was a trend – though not statistically significant – toward benefit with combination chemo-immunotherapy in the PD-L1-high subgroup, suggesting that the use of PD-L1 as a predictive biomarker might be useful in this clinical setting.
Objective response rates were similar between the arms, though the combination arm did achieve a higher rate of complete responses (13%) relative to the platinum plus placebo arm (7%).
With respect to the safety of the combination, the addition of atezolizumab does not appear to grossly alter the overall safety profile of the regimen, and the most common treatment-related adverse events were similar between the arms. A total of 34% of patients in both arms discontinued treatment for toxicity. Grade 5 events occurred in 9 patients (2%) in the combination arm and 4 patients (1%) in the chemotherapy plus placebo arm.
The most common immune-related adverse events were rash, hepatitis, and thyroid abnormalities, all of which skewed toward the chemo-immunotherapy combination arm. No new safety signal was identified.
IMvigor130 is the first positive randomized trial of chemo-immunotherapy in metastatic urothelial cancer. The combination of platinum-based chemotherapy with the immune checkpoint inhibitor atezolizumab is associated with an improvement in progression-free survival that is statistically significant. Overall survival data are not yet mature, though these data have the potential to become practice-changing in the future should the treatment arms continue to diverge in subsequent follow-up analyses.
Presented by: Enrique Grande, MD, MD Anderson Cancer Center, Madrid, Spain
Written by: Michael Lattanzi, MD, Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center, Twitter: @MikeLattanzi at the 2019 European Society for Medical Oncology Congress (#ESMO19), September 27 – October 1, 2019, Barcelona, Spain
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