Atezolizumab Moves to EU for Final Approval in Urothelial Carcinoma, NSCLC


The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has given its support on indications for atezolizumab (Tecentriq) in non–small cell lung cancer (NSCLC) and urothelial carcinoma. 

Sandra Horning, MD

Sandra Horning, MD

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has given its support on indications for atezolizumab (Tecentriq) in non—small cell lung cancer (NSCLC) and urothelial carcinoma.

Roche announced that the CHMP supports atezolizumab monotherapy for adults with previously-treated, locally advanced or metastatic NSCLC, and for adults with locally advanced or metastatic urothelial carcinoma who have been previously treated with a platinum based chemotherapy or who are ineligible for cisplatin chemotherapy.

The European Commission will now make a final approval decision on use of atezolizumab in the European Union for these indications.

“This positive CHMP opinion represents great news for people living with either advanced lung or bladder cancer because, despite recent developments, long-term survival rates for people with these cancers are inferior to those with other common cancers,” Sandra Horning, MD, Roche’s chief medical officer and head of global product development, said in a press release. “We are encouraged that the CHMP considered the totality of the data for Tecentriq, including the importance of key clinical endpoints, such as long-term responses.”

The CHMP based its opinion on results in NSCLC from the phase III OAK and the phase II POPLAR studies, and results from the phase III IMvigor211 and cohorts 1 and 2 from the single-arm phase II IMvigor210 studies in urothelial carcinoma.

OAK was a global, open-label, randomized, controlled trial comparing atezolizumab with docetaxel for efficacy and safety. Patients were assigned to 1200 mg atezolizumab every 3 weeks (n = 425) or 75 mg/m2IV of docetaxel administered every 3 weeks (n = 425).

Patients in the experimental arm saw a 4.2-month overall survival (OS) benefit compared with docetaxel (13.8 vs 9.6 months; hazard ratio [HR], 0.73; 95% CI, 0.62-0.87;P= .0003). Overall survival at 12 months (55% vs 41%) and 18 months (40% vs 27%) also favored the atezolizumab arm. Median time to OS events was 13.8 months in the experimental arm versus 9.6 months in the docetaxel arm.

Atezolizumab was also associated with superior OS in the international, randomized, open-label, controlled, phase II POPLAR study. Patients with advanced NSCLC previously treated with platinum-based chemotherapy (N = 287) were randomly assigned 1:1 to 1200 mg of atezolizumab every 3 weeks until loss of clinical benefit or 75 mg/m2of docetaxel on day 1 of each 3-week cycle until disease progression.

At a median survival follow-up of 22 months and a total of 200 observed deaths, median OS was 12.6 months in the atezolizumab arm compared with 9.7 months for patients assigned to docetaxel (HR, 0.69; 95% CI, 0.52-0.92). Overall response rate (ORR) was 15.3% vs. 14.7% favoring atezolizumab. Median duration of response (DOR) was 18.6 months versus 7.2 months in favor of atezolizumab.

Investigators evaluated the safety and efficacy of atezolizumab compared with vinflunine, paclitaxel or docetaxel in IMvigor 211 (N = 931). Patients with metastatic urothelial carcinoma who had progressed during or after platinum-based chemotherapy were eligible.

Investigators evaluated OS, the primary efficacy endpoint, successively in study populations defined by PD-L1 expression. The first population tested was patients with the highest levels of PD-L1 expression (tumor-infiltrating immune cells [IC]2/3), followed by those with any observable level of PD-L1 expression (IC1/2/3), and then the intent-to-treat population (ITT).

Atezolizumab failed to meet the primary endpoint in the study. Median OS in the IC2/3 (≥5%) group was 11.1 or atezolizumab versus 10.6 months for chemotherapy (HR, 0.87; 95% CI, 0.63-1.21). Median OS in the ITT population slightly favored atezolizumab, at 8.6 versus 8.0 months (HR, 0.85; 95% CI, 0.73-0.99).

The IC2/3 (≥5%) population needed to achieve statistical significance first, followed by the IC1/2/3 (≥1%) group, and the ITT group. Because statistical significance was not achieved for OS in the IC2/3 population, results could not be evaluated for statistical significance in the IC1/2/3 and ITT populations.

Patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy were eligible for IMvigor210.

ORR in cohort 1 (N = 119) was 22.7% for all-comers. In patients with ≥5% PD-L1 expression, ORR was 28.1%, and in patients with ≥1% PD-L1 expression, ORR was 23.8%. There were 11 (9.2%) complete responses and 16 (13.4%) partial responses.

In cohort 2 (N = 310), the coprimary efficacy endpoints were confirmed ORR as assessed by independent review using RECIST v1.1 and investigator-assessed ORR according to modified RECIST (mRECIST) criteria.

At a median duration of survival follow-up of 21.1 months, the confirmed ORRs per RECIST v1.1 were 28.0% (95% CI, 19.5-37.9) in patients with PD-L1 expression IC2/3 (≥5%), 19.3% (95% CI, 14.2-25.4) in patients with PD-L1 expression IC1/2/3 (≥1%), and 15.8% (95% CI, 11.9-20.4) in all-comers, the primary analysis population consisted of the first 850 randomized patients.

The confirmed ORR per investigator-assessed mRECIST was 29.0% (95% CI, 20.4-38.9) in patients with PD-L1 expression ≥5%, 23.7% (95% CI, 18.1-30.1) in patients with PD-L1 expression ≥1%, and 19.7% (95% CI, 15.4-24.6) in all-comers. The rate of complete response per RECIST v1.1 in the all-comer population was 6.1% (95% CI, 3.7-9.4).

For cohort 2, median DOR was not reached in any PD-L1 expression subgroup or in all-comers. However, patients with PD-L1 expression <1% did reach median DOR (13.3 months; 95% CI 4.2-not reached). The OS rate at 12 months was 37% in all-comers.

Safety results are based on pooled data in 2160 patients with metastatic urothelial carcinoma and NSCLC. The most common adverse all grade reactions were fatigue (35.4%), decreased appetite (25.5%), nausea (22.9%), dyspnea (21.8%), diarrhea (18.6%), pyrexia (18.3%), rash (18.6%), vomiting (15.0%), arthralgia (14.2%), asthenia (13.8%) and pruritus (11.3%).


CHMP recommends EU approval for Roche&rsquo;s TECENTRIQ (atezolizumab) in a specific type of metastatic lung and two types of metastatic bladder cancer. Roche website. Accessed July 21, 2017.

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