Efficacy of Frontline Atezolizumab Combo Is Comparable Regardless of Primary Urothelial Cancer Location

An exploratory analysis of the phase 3 IMvigor130 trial (NCT02807636) demonstrated that the benefit of frontline atezolizumab (Tecentriq) added to gemcitabine and platinum chemotherapy was maintained in patients with urothelial cancer, regardless of the site of the primary tumor.

“These results suggest that both upper tract and lower tract primaries derive similar benefit from combination therapy with atezolizumab and chemotherapy,” Aristotelis Bamias, MD, said in a presentation at the 12th European Multidisciplinary Congress on Urological Cancers. Bamias is an associate professor at the University of Athens School of Medicine in Greece.

The randomized study compared atezolizumab plus chemotherapy (arm A) with atezolizumab monotherapy (arm B) or placebo/chemotherapy (arm C) as frontline treatment of patients with metastatic urothelial carcinoma. Progression-free survival (PFS) superiority in arm A versus arm C, one of the coprimary end points, had been met (HR, 0.82; 95% CI, 0.70-0.96; 1-sided P=.007). Interim overall survival (OS) analysis for the same 2 arms exhibited a trend toward superiority with the experimental regimen, but these data failed to reach statistical significance (stratified HR, 0.83; 95% CI, 0.69-1.00; P=.027).² Final OS data have yet to be read out.

“In this exploratory analysis, we aimed to determine whether primary tumor site would affect treatment outcomes between arms A and C,” Bamias said.

Patient baseline characteristics indicated that most patients in both arms had lower tract disease (arm A, n=322; arm C, n=298), with bladder cancer accounting for over 95% of all cases. In patients with upper tract cancers (arm A, n=123; arm C, n=100), disease sites were evenly distributed between renal pelvis and ureter.

More patients with upper tract disease were cisplatin ineligible versus those with lower tract disease in arm A (66% vs 55%, respectively) and arm C (61% vs 53%); baseline impaired renal function was also higher in this group for both arms (arm A, 61% vs 44%; arm C, 55% vs 49%). Otherwise, baseline characteristics were balanced between patients.

“There were numerical differences [in charac-teristics] between arms A and C in upper tract disease,” Bamias said. “Patients in arm C had more frequent liver metastases, whereas patients in arm A had [a higher rate] of ECOG performance status 0 and more [cases] of higher PD-L1 expression.

”Hazard ratios for PFS and OS regardless of tumor site favored atezolizumab plus chemotherapy, and these results were consistent after adjusting for covariates of prognostic significance, such as ECOG performance status, the presence of liver metastases, PD-L1 expression, cisplatin eligibility status, and choice of platinum chemotherapy.

In upper tract disease, the median PFS in arm A was 8.2 months versus arm C at 6.2 months (HR, 0.69; 95% CI, 0.51-0.94). The corresponding median OS was 16.9 months versus 13.5 months (HR, 0.78; 95% CI, 0.54-1.12).

In patients with lower tract tumors, the median PFS was 8.1 months in arm A compared with 6.5 months in arm C (HR, 0.85; 95% CI, 0.70-1.02); the median OS in both arms was 15.8 months versus 13.4 months (HR, 0.87; 95% CI, 0.70-1.08).

Efficacy by response was similar between upper and lower tract tumors. However, the median duration of response appeared to be longer in upper tract disease versus lower tract disease. However, Bamias pointed out that tumors from either location favored therapy with atezolizumab versus placebo (TABLE).

Tolerability of the atezolizumab regimen was acceptable in patients with lower and upper tract urothelial cancer, and no increases in toxicity were observed in either group versus chemotherapy.

The investigators led by Bamias wrote in their presentation that although these results indicate benefit for both groups, underlying primary tumor site may still impact the efficacy of the atezolizumabregimen and warrants further study.

REFERENCES

1.Bamias A, De Santis M, Grande E, et al. A subgroup analysis from the IMvigor130 study in patients with upper tract vs. lower tract locally ad-vanced or metastatic urothelial carcinoma treated with atezolizumab plus platinum-based chemotherapy. Presented at: 12th European Multidisci-plinary Congress on Urological Cancers; November 13-14, 2020; virtual. Abstract 05. Accessed December 16, 2020. https://bit.ly/3nCrT0I

2.Galsky MD, Arija JÁA, Bamias A, et al; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10236):1547-1557. doi:10.1016/S0140-6736(20)30230-0