FDA Approves 2 Therapies for Treatment of Metastatic Non–Small Cell Lung Cancer

The FDA approved 2 new therapies, each with its own companion diagnostic, for the treatment of patients with metastatic non–small cell lung cancer (mNSCLC).

Atezolizumab Approved as Frontline Monotherapy

Atezolizumab (Tecentriq) was granted approval as a frontline monotherapy to treat adults with mNSCLC whose tumors have high PD-L1 expression (PD-L1–stained ≥50% of tumor cells [TCs] or PD-L1–stained tumor-infiltrating cells [ICs] covering ≥10% of the tumor area), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.¹

The Ventana PD-L1 (SP142) assay (Roche) was granted approval as a companion diagnostic device for selecting patients with NSCLC for treatment with atezolizumab.

Approval for atezolizumab, the first and only single-agent cancer immunotherapy with 3 dosing options, was based on an interim analysis from the phase 3 IMpower110 study. IMpower110 is a randomized, open-label trial evaluating 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 nonsquamous or squamous NSCLC.

The study enrolled 572 participants, of which 554 were in the intent-to-treat TC3/IC3–wild-type population. Participants were randomized 1:1 to receive either atezolizumab monotherapy or platinum-based chemotherapy. Treatment continued until disease progression, unacceptable toxicity, or death.

Data analysis showed that atezolizumab monotherapy improved overall survival (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 = .0106) in individuals with high PD-L1 expression.

Treatment-related adverse events (AEs) were reported in 12.9% of patients receiving atezolizumab, compared with 44.1% of those receiving chemotherapy. No new safety signals were reported for atezolizumab, which has already received 4 approvals across various NSCLC indications, either as a single agent or in combination with other targeted therapies and/or chemotherapies. Atezolizumab is also approved in combination with carboplatin and etoposide as a first-line treatment for adult patients with extensive-stage small cell lung cancer.²

The primary end point for the study was OS by PD-L1 subgroup, as determined by the SP142 assay test. Median progression-free survival (PFS), a secondary end point for the study, was 8.1 months (95% CI, 6.8-11.0) in the atezolizumab arm and 5.0 months (95% CI, 4.2-5.7) in the chemotherapy arm (HR, 0.63; 95% CI, 0.45-0.88). Confirmed overall response rates (ORRs) were 38% (95% CI, 29%-48%) and 29% (95% CI, 20%-39%), respectively.

The recommended atezolizumab dosage for treatment of NSCLC is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks, administered intravenously over 60 minutes.

Nivolumab Plus Ipilimumab Approved With Companion Diagnostic

The FDA also approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) as a first-line treatment for patients with mNSCLC whose tumors express PD-L1 (≥1%), as determined by the PD-L1 IHC 28-8 pharmDx companion diagnostic (Agilent), with no EGFR or ALK genomic tumor aberrations. The diagnostic tool was newly approved by the FDA as well.³

Approval was based on results of the CheckMate 227 trial, which was designed to evaluate the combination treatment in patients with metastatic or recurrent NSCLC and no prior anticancer therapy. In part 1a of the trial, 793 participants were randomized to either nivolumab plus low-dose ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397).

The study results demonstrated an improvement in OS for patients with PD-L1 tumor expression 1% ir greater receiving the combination of nivolumab plus ipilimumab compared with those in the chemotherapy arm. Median OS was 17.1 months (95% CI, 15.0-20.1) versus 14.9 months (95% CI, 12.7-16.7) (HR, 0.79; 95% CI, 0.67-0.94; P = .0066).

Median PFS, per blinded independent central review (BICR), was 5.1 months (95% CI, 4.1-6.3) in the combination arm and 5.6 months (95% CI, 4.6-5.8) in the chemotherapy arm (HR, 0.81; 95% CI, 0.69-0.97). ORRs as assessed by BICR were 36% (95% CI, 31%-41%) and 30% (95% CI, 26%-35%), respectively.

Median duration of response for patients receiving nivolumab plus ipilimumab was 23.2 months, compared with 6.2 months for those receiving chemotherapy.

Fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis were the most commonly observed AEs, with 20% or greater participants reporting these toxicities.

The FDA-recommended dosages for metastatic NSCLC treatment are 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

REFERENCES

1. FDA approves atezolizumab for first-line treatment of metastatic NSCLC with high PD-L1 expression. FDA. May 18, 2020. Accessed May 20, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-first-line-treatment-metastatic-nsclc-high-pd-l1-expression

2. FDA approves Genentech’s Tecentriq as a first-line monotherapy for certain people with metastatic non-small cell lung cancer. News release. Genentech. May 18, 2020. Accessed May 20, 2020. http://www.gene.com/media/press-releases/14850/2020-05-18/fda-approves-genentechs-tecentriq-as-a-f

3. FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%). FDA. May 15, 2020. Accessed May 20, 2020. http://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-ipilimumab-first-line-mnsclc-pd-l1-tumor-expression-1