June 25, 2020
4 min read

FDA approves four NSCLC regimens

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The FDA approved four regimens for non-small cell lung cancer since mid-May.

An overview of the approvals follows.


The FDA expanded the approval of atezolizumab (Tecentriq, Genentech) to include first-line monotherapy of patients with metastatic NSCLC whose tumors have high PD-L1 expression.

The approval applies to use of atezolizumab by patients who have no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

This is the fourth indication in metastatic NSCLC and fifth overall in lung cancer for atezolizumab, a monoclonal antibody designed to bind with PD-L1.

The FDA based the new indication on results of an interim analysis of the randomized phase 3 IMpower110 study, which enrolled 572 PD-L1-selected patients with chemotherapy-naive, stage IV nonsquamous or squamous NSCLC who had no EGFR or ALK genomic tumor aberrations.

Researchers assigned patients 1:1 to atezolizumab monotherapy or chemotherapy, followed by maintenance therapy with pemetrexed alone or best supportive care.

OS by PD-L1 subgroup served as the primary efficacy endpoint. Key secondary endpoints included investigator-assessed PFS, objective response rate and duration of response.

Results showed longer median OS with atezolizumab among patients with high PD-L1 expression (20.2 months vs. 13.1 months; HR = 0.59; 95% CI, 0.4-0.89). Grade 3 or grade 4 treatment-related adverse events occurred among 12.9% of patients assigned atezolizumab and 44.1% of those assigned chemotherapy.


The FDA approved brigatinib (Alunbrig, Takeda) for first-line treatment of adults with ALK-positive metastatic NSCLC.

Brigatinib is a next-generation tyrosine kinase inhibitor designed to target ALK molecular alterations, found among 3% to 5% of patients with metastatic NSCLC.

The FDA previously approved brigatinib for treatment of patients with ALK-positive metastatic NSCLC who progressed on or could not tolerate crizotinib (Xalkori; Pfizer, EMD Serono).

The agency based the first-line indication on results of the randomized phase 3 ALTA 1L trial, which included 275 adults with ALK-positive locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor.

Researchers assigned 137 patients to brigatinib dosed at 180 mg once daily, with a 7-day lead-in at 90 mg once daily. The other 138 patients received crizotinib dosed at 250 mg once daily.

PFS assessed by blinded independent review served as the major efficacy outcome.

After more than 2 years of follow-up, results showed improved PFS (median, 24 months vs. 11 months; HR = 0.49) among brigatinib-treated patients. Among patients with measurable brain metastases at baseline, a higher percentage of those treated with brigatinib than crizotinib achieved confirmed intracranial response (78% vs. 26%).

The most common adverse reactions among brigatinib-treated patients included diarrhea (53%), rash (40%), cough (35%), hypertension (32%), fatigue (32%) and nausea.


One-third (33%) of patients assigned brigatinib experienced serious adverse events, the most common of which were pneumonia (4.4%), interstitial lung disease/pneumonitis (3.7%) and pyrexia (2.9%). Also, 2.9% of patients experienced fatal adverse reactions other than disease progression; these included pneumonia (1.5%), cerebrovascular accident (0.7%) and multiple organ dysfunction syndrome (0.7%).

D. Ross Camidge

“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for [patients with ALK-positive lung cancer] that have proven to be superior to crizotinib,” D. Ross Camidge, MD, PhD, Joyce Zeff chair in lung cancer research at University of Colorado Cancer Center, said in a press release. “Compared to crizotinib, brigatinib demonstrated superior efficacy — especially among those with brain metastases at baseline — and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years.”


The FDA expanded the approval of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) combined with limited chemotherapy as first-line treatment of adults with metastatic or recurrent NSCLC who do not have EGFR or ALK genomic tumor aberrations.

Nivolumab is an anti-PD-1 antibody. Ipilimumab is an anti-CTLA-4 antibody.

The regimen covered by this approval is nivolumab dosed at 360 mg plus IV ipilimumab dosed at 1 mg/kg given with two cycles of platinum-doublet chemotherapy. It is indicated for patients with squamous or nonsquamous disease, regardless of PD-L1 expression.

The FDA based the approval on results of the randomized phase 3 CheckMate -9LA trial, which included 719 patients with metastatic or recurrent NSCLC.

Researchers assigned 361 patients to first-line treatment with nivolumab plus ipilimumab combined with two cycles of platinum-doublet chemotherapy. The other 358 patients received four cycles of platinum-doublet chemotherapy, followed by optional pemetrexed maintenance therapy if eligible. Treatment continued until disease progression or toxicity.

OS served as the primary efficacy outcome. Results of a prespecified interim analysis performed after minimum follow-up of 8.1 months showed patients assigned nivolumab plus ipilimumab achieved longer OS (median, 14.1 months vs. 10.7 months; HR = 0.69; 96.71% CI, 0.55-0.87). A follow-up analysis at 12.7 months showed even greater OS benefit with the combination (median, 15.6 months vs. 10.9 months; HR = 0.66; 95% CI, 0.55-0.8). More patients assigned the nivolumab-ipilimumab regimen remained alive at 1 year (63% vs. 47%).

David P. Carbone

“We have come a long way in understanding the role of dual immunotherapy-based approaches in cancer and the potential impact on patients’ long-term outcomes,” study investigator David P. Carbone, MD, PhD, director of the James Thoracic Oncology Center at The Ohio State University, said in a Bristol-Myers Squibb-issued press release. “The positive findings from CheckMate -9LA demonstrate the benefit of combining dual immunotherapy with limited chemotherapy for [patients with NSCLC] regardless of PD-L1 status.”


The most common adverse reactions included fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%) and rash (30%). The most frequent serious adverse events included pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis and respiratory failure.

Seven patients (2%) experienced fatal adverse events. These included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia and massive hemoptysis in the setting of thrombocytopenia.


The FDA approved ramucirumab (Cyramza, Eli Lilly) in combination with erlotinib (Tarceva, Genentech) for first-line treatment of patients with metastatic NSCLC who have EGFR exon 19 deletions or exon 21 L858R mutations.

Ramucirumab is a fully human monoclonal antibody. Erlotinib is an EGFR TKI.

The FDA based the approval on results of the randomized phase 3 RELAY trial, which included 449 treatment-naive patients with metastatic NSCLC whose tumors had EGFR exon 19 deletion or exon 21 L858R mutations.

Researchers assigned patients 1:1 to erlotinib dosed at 150 mg daily plus either ramucirumab dosed at 10 mg/kg or placebo every 2 weeks. Treatment continued until disease progression or unacceptable toxicity. Investigator-assessed PFS served as the primary endpoint.

Researchers reported significantly longer median PFS (19.4 months vs. 12.4 months; HR = 0.59; 95% CI, 0.46-0.76) and median duration of response (18 months vs. 11 months) in the ramucirumab group.

The most common adverse events reported among patients assigned the ramucirumab-erlotinib combination included infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis and peripheral edema.