SYDNEY — There was no clinical benefit from adding cetuximab (Erbitux) to chemoradiation in patients with unresectable stage III non-small cell lung cancer (NSCLC) in the RTOG 0617 trial, and there was more toxicity.
Reporting the finding here at the plenary session of the 15th World Conference on Lung Cancer, Gregory Masters, MD, medical oncologist at the Helen Graham Cancer Center in Newark, Delaware, said: "Cetuximab should not be considered a standard component in the treatment of stage III NSCLC patients."
This is the second negative result from the RTOG 0617 trial. Previous results showed that a higher dose of radiation (74 Gy) was not better, and may be worse, than the standard dose (60 Gy).
Both of the negative results were surprising. The addition of cetuximab to chemoradiation and increasing the radiation dose had both been expected to improve on survival and local control of disease. But neither did.
High Hopes Dashed by Results
The results on the higher radiation dose were presented earlier this year at the American Society of Clinical Oncology annual meeting, and were "really astonishing," commented Jacek Jassem, MD, from the Medical University of Gdansk, Poland. There was worse local control of disease and worse adverse events when compared with standard-dose radiation, he noted.
Now comes news of the failure of cetuximab, even though there was a strong rationale from preclinical studies to expect that it would improve the response to radiation, he said in his discussion of the study.
Dr. Masters also commented that there was a high expectation for cetuximab to succeed, as there had been promising results from the earlier RTOG 0324 study, which showed improved efficacy when cetuximab was added to chemoradiation.
The RTOG 0617 results, however, tell a different tale. The addition of cetuximab had no significant effect on either overall survival or progression-free survival, but it significantly increased the overall rate of adverse events.
The cetuximab analysis was carried out on 465 patients, with a median follow-up of 18.7 months. Cetuximab was given as a loading dose of 400 mg/m², followed by weekly doses of 50 mg/m², added to chemotherapy with carboplatin and docetaxel, given concurrently with radiation.
Median overall survival for patients treated with chemoradiation with cetuximab was 23.1 months vs 23.5 months without cetuximab, and the 18-month overall survival rates were 60.8% vs 60.2%, respectively (P = .484; hazard ratio, 0.99). The median progression-free survival was 10.4 months with cetuximab vs 10.7 months without cetuximab.
Overall combined adverse events were reported by 85.2% of patients treated with chemoradiation with cetuximab vs 69.5% without cetuximab, while overall nonhematological adverse events were reported by 70.5% vs 50.7% of patients, respectively (both P < .0001).
"There was no apparent clinical efficacy with the current schedule of cetuximab, and there was excessive toxicity," Dr. Masters concluded.
Benefit in Subgroup?
Cetuximab is a monoclonal antibody targeting epidermal growth-factor receptor (EGFR). There was a suggestion that patients who had a higher expression of EGFR in their tumors (as measured on the H score by immunohistochemistry) had a better response that patients with low expression, Dr. Masters commented.
This has been reported previously in the FLEX study, which also found a better response to cetuximab in patients with high EGFR expression, but in that trial this better response was associated with only slightly better improved overall survival.
"Most of these tumors express EGFR," commented Dr. Jassem. "If we want to claim that patients do really benefit, then we need another prospective study."
15th World Conference on Lung Cancer (WCLC): Abstract PL03. Presented October 29, 2013.
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