FDA Approves Atezolizumab for PD-L1 High NSCLC

The FDA has approved single-agent atezolizumab (Tecentriq) as a first-line treatment for adult patients with metastatic non—small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

High PD-L1 expression is defined as PD-L1 stained ≥ 50% of tumor cells (TC ≥ 50%) or PD-L1 stained tumor-infiltrating (IC) covering ≥10% of the tumor area (IC ≥ 10%). The approval is based on findings from the phase III IMpower110 trial, which showed that atezolizumab monotherapy demonstrated a 7.1-month improvement in overall survival (OS) versus chemotherapy, with a median OS of 20.2 months and 13.1 months, respectively (HR, 0.59; 95% CI, 0.40-0.89; P = .0106) in patients with NSCLC and high PD-L1 expression.

“We are pleased to offer people with certain types of lung cancer a new chemotherapy-free option that can help prolong their lives and be administered on a flexible dosing schedule, including an option for once-a-month Tecentriq infusions,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, stated in a press release. “Today marks the fifth approval of Tecentriq in lung cancer, as we remain committed to providing an effective and tailored treatment option for every person diagnosed with this disease.”

In the open-label, randomized, phase III IMpower110 study, investigators randomized 572 PD-L1—selected, chemotherapy-naïve patients with advanced nonsquamous or squamous NSCLC without ALK or EGFR mutations 1:1 to receive single-agent atezolizumab (arm A) or cisplatin or carboplatin plus pemetrexed or gemcitabine (arm B). Atezolizumab was administered until loss of clinical benefit, unacceptable toxicity or death, or per investigator discretion.

For nonsquamous disease, chemotherapy regimens consisted of cisplatin at 75 mg/m² or carboplatin area under the curve (AUC) 6, plus pemetrexed at 500 mg/m² intravenously every 3 weeks. Patients with squamous histology who were on the chemotherapy arm received cisplatin at 75 mg/m² plus gemcitabine at 1250 mg/m², or carboplatin AUC 5 plus gemcitabine at 1000 mg/m² intravenously every 3 weeks.

Maintenance therapy consisted of atezolizumab in arm A and pemetrexed (nonsquamous) or best supportive care (squamous) in arm B. No crossover was permitted.

The primary endpoint was OS by PD-L1 subgroup (TC3/IC3-WT; TC2/3/ IC2/3-WT; and TC1/2/ 3/IC1/2/3-WT), as determined by the SP142 assay. Key secondary endpoints include investigator-assessed progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR).

The primary endpoint of OS was tested hierarchically in WT patients (TC3 or IC3, then TC2/3 or IC2/3, then TC1/2/3 or IC1/2/3); a total of 205 patients were TC3 or IC3 WT. The secondary endpoint of PFS would only be formally tested if the primary endpoint was positive among all 3 TC/IC cohorts.

The OS testing boundary was not crossed in the TC2/3 or IC2/3 WT population, so OS was not formally tested in this population as well as in the TC1/2/3 and IC1/2/3 populations.

Baseline characteristics were well balanced between the arms, including in the TC3 or IC3 subset. About half of the patients overall were <65 years old, about 70% were male, >80% were white, and 13% never used tobacco. Approximately 70% in both arms had nonsquamous histology.

In arm A, 38.6% of patients were TC3 or IC3 WT, compared with 35.4% of patients in arm B. Some 59.9% in arm A and 58.5% in arm B were TC2/3 or IC2/3 (≥5% expression on tumor cells or immune cells) wild type.

In the TC3/IC3 wild-type population, 76.3% in arm A and 70.1% in arm B were alive at 6 months, and the 12-month OS rates were 64.9% and 50.6%, respectively. Subset analysis showed a consistent benefit on OS favoring atezolizumab in all subgroups with TC3 or IC3 wild type, except for in those who had never used tobacco.

In the TC 2/3 or IC 2/3 wild-type subgroup, median OS was 18.2 months (95% CI, 13.3-not evaluable) in the atezolizumab arm versus 14.9 months (95% CI, 10.8-16.6) in the chemotherapy arm (HR, 0.72; 95% CI, 0.52-0.99; P = .0416). OS also favored atezolizumab in the TC 1/2/3 or IC 1/2/3 wild-type population but was not found to be significant (HR, 0.83; 95% CI, 0.65-1.07; P = .1481).

Additionally, 29.6% of patients in the atezolizumab arm and 49.5% in the chemotherapy had ≥1 subsequent cancer therapy, and 28.9% in the chemotherapy arm ultimately received a form of immunotherapy.

In the TC3 or IC3 WT population, the 6-month PFS rate was 59.8% in arm A and 38.3% in arm B, and at 12 months, 36.9% in arm A were without disease progression compared with 21.6% in arm B. PFS was numerically superior in the atezolizumab arm in the TC2/3 or IC2/3 and TC1/2/3 or IC1/2/3 subgroups, although the statistical significance could not be tested.

Regarding safety, TRAEs occurred in 60.5% (arm A) and 85.2% (arm B) of patients.

FDA Approves Genentech’s Tecentriq as a First-Line Monotherapy for Certain People With Metastatic Non-Small Cell Lung Cancer. Published May 18, 2020. https//bit.ly/2AGRNNh. Accessed May 18, 2020.