FDA Approves Atezolizumab as a First-Line Treatment for Metastatic NSCLC Subgroup

May 18, 2020

Atezolizumab was approved as a first-line treatment for adults with metastatic non-small cell lung cancer whose tumors have high PD-L1 expression, as determined by an FDA approved test, with no EGFR or ALK genomic tumor aberrations.

The FDA approved atezolizumab (Tecentriq) as the first and only single-agent cancer immunotherapy with 3 dosing options, allowing administration every 2, 3, or 4 weeks, according to Genentech, the developer of the agent.

In particular, the agent is approved as a frontline monotherapy to treat adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating [IC] covering ≥ 10% of the tumor area [IC ≥ 10%]), as determined by an FDA approved test, with no EGFR or ALK genomic tumor aberrations. 

“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 (atezolizumab) infusions,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “Today marks the fifth approval of (atezolizumab) in lung cancer, as we remain committed to providing an effective and tailored treatment option for every person diagnosed with this disease.”

The approval was based on an interim analysis from the randomized, open-label, phase III IMpower110 study, designed to evaluate the efficacy and safety of atezolizumab monotherapy compared with cisplatin or carboplatin and pemetrexed or gemcitabine in PD-L1-selected, chemotherapy-naïve patients with stage IV non-squamous or squamous NSCLC. 

Overall, 572 participants were enrolled in the study, 554 of which were in the intent-to-treat TC3/IC3-wild-type population, which excluded those with EGFR or ALK genomic tumor aberrations, and were randomized in a 1:1 fashion to receive either atezolizumab monotherapy or chemotherapy. Those in the chemotherapy arm received cisplatin or carboplatin, per investigator discretion, combined with either pemetrexed for the non-squamous cohort or gemcitabine for the squamous cohort. This was followed by maintenance therapy with pemetrexed alone for the non-squamous group or best supportive care for the squamous group. All treatment was administered until disease progression, unacceptable toxicity, or death.

The primary endpoint for the study was overall survival (OS) by PD-L1 subgroup, as determined by the SP142 assay test. Secondary endpoints included investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). 

The study demonstrated that atezolizumab monotherapy improved OS by 7.1 months compared with chemotherapy (median OS, 20.2 months vs 13.1 months; HR, 0.59; 95% CI, 0.40-0.89; P = 0.0106) in individuals with high PD-L1 expression.

Safety for atezolizumab appeared to be consistent with its known safety profile, and no new safety signals were reported. Moreover, grade 3 to 4 treatment-related adverse events were reported in 12.9% of patients receiving atezolizumab, compared with 44.1% of those receiving chemotherapy. 

In the US, atezolizumab has already received 4 approvals across NSCLC indications, as a single agent or in combination with targeted therapies and/or chemotherapies. Additionally, atezolizuamb is approved in combination with carboplatin and etoposide for the first-line treatment of adults with extensive-stage SCLC. 

Genentech indicated that they also have multiple ongoing and planned phase III studies of atezolizumab, as a monotherapy or in combination regimens, across lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. 

Reference:

FDA Approves Genentech’s Tecentriq as a First-Line Monotherapy for Certain People with Metastatic Non-Small Cell Lung Cancer [news release]. South San Francisco, California. Published May 18, 2020. gene.com/media/press-releases/14850/2020-05-18/fda-approves-genentechs-tecentriq-as-a-f. Accessed May 18, 2020.