Updated IMvigor130 data shows OS benefit of atezolizumab for bladder cancer

Updated analyses of the phase III IMvigor130 trial presented at AACR 2021 revealed the overall survival (OS) benefit of atezolizumab for previously untreated locally advanced or metastatic urothelial carcinoma (mUC), be it alone or with platinum/gemcitabine chemotherapy (CT).

The study comprised 1,213 participants (median age 67.6 years, 75 percent male) who were randomized 1:1:1 to receive either atezolizumab + platinum/gemcitabine CT (arm A), atezolizumab monotherapy (arm B), or placebo + platinum/gemcitabine CT (arm C). IV gemcitabine 1,000 mg/m² BSA* was administered on days (D)1 and 8 of each 21-day cycle, plus IV carboplatin (AUC** 4.5 mg/mL/min) or IV cisplatin 70 mg/m² BSA (D1 of each cycle), with either IV atezolizumab 1,200 mg (D1 of each cycle) or placebo. [Lancet 2020;395:1547-1557]

 

Arms A vs C: Atezolizumab + platinum/gemcitabine

After the second interim OS analysis (median follow-up 13.3 months), the hazard ratio (HR) for OS was 0.84 (p_one-sided=0.026) in favour of arm A. While not statistically significant, these results correlate with the first interim analysis. [AACR 2021, abstract CT042]

“The impact of atezolizumab-CT on outcomes may differ based on the specific platinum regimen,” noted the researchers, as reflected by the HRs when stratified by CT used (HRs, 0.73 and 0.91 for cisplatin and carboplatin, respectively). A similar trend was observed when further stratification was done by PD-L1 IC*** status, both for cisplatin (HRs, 0.66 and 0.72 for IC2/3 and IC0/1, respectively) and carboplatin (HRs, 0.80 and 0.94, respectively).

Both arms A and C had similar objective response rates (ORR, 48 percent vs 45 percent) and median duration of responses (DOR, 9.3 vs 8.2 months).

The safety profile observed in arm A was consistent with that reported for each agent. The rates of grade 3/4 adverse events of special interest (AESIs) were twice as high in arm A vs C (9 percent vs 4 percent) but treatment-related AE (TRAE) rates were similar (81 percent vs 80 percent).

Despite the lack of statistical significance, these findings boost the encouraging OS results initially reported, noted the researchers.

 

Arms A vs C: OS during induction

A post hoc analysis looked into OS outcomes in arm A and C participants who completed 4–6 (but not >6) CT cycles without progressive disease (PD) during induction (through week 18), followed by ≥1 dose of atezolizumab or placebo maintenance. [AACR 2021, abstract CT187]

In terms of OS, HRs favoured arm A over C, both during post-induction among those without PD (HR, 0.86) and post-progression in patients with PD (HR, 0.74).

“[These findings suggest that the] OS benefit with atezolizumab-CT vs placebo-CT in both patients with and without PD during induction was consistent with the ITT^# results from the first interim analysis,” said the researchers.

Stratification by CT type appeared to favour cisplatin over carboplatin among participants with (HR, 0.52 vs 0.78) and without PD (HR, 0.60 vs 0.97). “[These findings imply that] cisplatin recipients may derive greater OS benefit from adding atezolizumab to CT than carboplatin recipients, which warrants further investigation,” they added.

 

Arm B vs C: Atezolizumab monotherapy

In another analysis, OS was longer in arm B vs C participants with IC2/3 (median, 27.5 vs 16.7 months; HR, 0.67), and those with IC2/3 who were cisplatin-ineligible (median, 18.6 vs 10.0 months; HR, 0.60). In the ITT cohort, ORR was lower (23.4 percent vs 44.1 percent) but median DOR was longer in arm B vs C (29.6 vs 8.1 months). [AACR 2021, abstract CT040]

Atezolizumab monotherapy also showed a better tolerability profile than CT, as reflected by the fewer grade 3/4 TRAEs (16 percent vs 80 percent) in arm B vs C. No new safety concerns were reported.

“These [findings] support the benefit of atezolizumab monotherapy as first-line treatment for PD-L1 IC2/3 cisplatin-ineligible mUC,” said the researchers.

OS follow-up is ongoing to ascertain these interim findings.