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Cetuximab may benefit select patients with NSCLC
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The addition of cetuximab to chemotherapy failed to improve outcomes in the overall population of patients with non–small cell lung cancer, according to the results of a randomized phase 3 trial presented at the World Conference on Lung Cancer.
However, cetuximab (Erbitux; Bristol-Myers Squibb, Lilly) conferred benefit for certain patients positive for the epidermal growth factor receptor gene copy number measured by fluorescent in situ hybridization (FISH), as well as patients with squamous carcinoma.
Roy S. Herbst
“Our hypothesis was that patients who had more than four copies of the EGFR gene were more likely to benefit from this therapy,” Roy S. Herbst, MD, PhD, Ensign professor of medicine (medical oncology) and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, said during a press conference.
Herbst and colleagues from Southwest Oncology Group conducted a multicenter, open label phase 3 trial that enrolled patients with newly diagnosed or recurrent stage IV NSCLC. The researchers required that all patients have tumor tissue available for EGFR FISH testing.
The final analysis included data from 1,313 patients. The researchers determined EGFR FISH status in 976 patients, of whom 41% (n = 400) were designated FISH-positive. Approximately 25% of patients had squamous carcinoma.
Researchers stratified patients by their appropriateness to bevacizumab (Avastin, Genentech), smoking status and M-substage.
The researchers randomly assigned patients to a treatment regimen of carboplatin and paclitaxel
with (n = 656) or without (n = 657) concurrent cetuximab. Bevacizumab-inappropriate patients comprised 57% (n = 377) of the cetuximab arm and 58% (n = 382) of the control arm.
PFS in FISH-positive patients and OS in the overall study population served as the primary endpoints. Secondary endpoints included OS in FISH-positive patients, as well as the comparison of clinical outcomes among bevacizumab-appropriate vs. -inappropriate patients.
The researchers did not observe a significant benefit with the addition of cetuximab for PFS (HR = 0.98; 95% CI, 0.87-1.09) or OS (HR = 0.94; 95% CI, 0.84-1.06) in the overall study population. A slight PFS (HR = 0.91; 95% CI, 0.71-1.12) and OS (HR = 0.83; 95% CI, 0.67-1.04) benefit occurred among FISH-positive patients; however, Herbst noted that these improvements did not reach statistical significance.
However, the addition of cetuximab significantly prolonged OS for bevacizumab-inappropriate, FISH-positive patients (HR = 0.75; 95% CI, 0.57-1), as well as patients with squamous carcinoma (HR = 0.56; 95% CI, 0.37-0.84).
Overall, cetuximab was well tolerated, with reported adverse events consistent with prior reports.
“Patients with squamous cell carcinoma are very difficult to treat, and there have been very few new drugs for this group in the last decade,” Herbst said. “This is the most compelling finding of the study.” – by Cameron Kelsall
Reference:
Herbst R, et al. A randomized, phase III study comparing carboplatin/paclitaxel or carboplatin/paclitaxel/bevacizumab with or without concurrent cetuximab in patients with advanced non–small cell lung cancer (NSCLC): SWOG S0819. Presented at: 16th World Conference on Lung Cancer; Sept. 6-9, 2015; Denver, Colorado.
Disclosure: Herbst reports consultant roles with Bristol-Myers Squibb, Eli Lilly, Genentech, Merck and Pfizer, as well as scientific advisory roles with Biothera, Diatech and Koltan. HemOnc Today was unable to obtain a list of the other researchers’ relevant financial disclosures at the time of reporting.