Cetuximab Fails To Increase Chemoradiation OS In Oesophageal Cancer Patients

Combining chemoradiation with cetuximab does not benefit patients with oesophageal cancer undergoing a nonsurgical treatment approach

medwireNews: Overall survival (OS) in patients with oesophageal cancer is not boosted by the addition of the epidermal growth factor receptor (EGFR) inhibitor cetuximab to a nonsurgical chemoradiation regimen, a phase III study shows.

At 24 months, 45% of the 159 patients were alive after receiving concurrent cisplatin 50 mg/m2 with paclitaxel 25 mg/m2 and 50.4 Gy of radiation in daily 1.8 Gy fractions, alongside cetuximab 400 mg/m2 on day 1 followed by a weekly dose of 250 mg/m2.

This did not significantly differ from the 44% OS rate at 24 months for the 169 patients given the chemoradiation regimen alone. Nor did the OS rate at 36 months differ between the cetuximab and control groups, at 34% versus 28%.

“The results of the NRG Oncology RTOG 0436 trial are consistent with other phase 3 studies that have failed to demonstrate OS improvements with the addition of EGFR inhibition to concurrent chemoradiation regimens for various solid tumors”, say Mohan Suntharalingam, from The University of Maryland School of Medicine in Baltimore, USA, and co-investigators in JAMA Oncology.

Citing data from the SCOPE 1 and REAL 3 studies, they write: “Taken together, these trial results highlight the need to identify prognostic variables that may provide insight into which patient populations will benefit from EGFR inhibition.”

The NRG Oncology RTOG 0436 trial was open to patients with squamous cell or adenocarcinoma of the oesophagus or gastro-oesophageal junction at stage T1N1M0 or T2–T4 with any N or M stage, the researchers explain, noting that the treatment arms were well matched for T3 or T4 disease and node status.

Overall, 56% of patients given cetuximab plus chemoradiation achieved a clinical complete response, as did 58% of those given chemoradiation only; neither arm showed a difference in response by histology.

After a median of 18.6 months, the 24-month rate of local failure was a comparable 47% with the cetuximab combination versus 49% with chemoradiation only.

For patients given cetuximab plus chemoradiation, grade 3, 4 and 5 treatment-related adverse events occurred in 46%, 23% and 4%, with corresponding rates of 50%, 17% and 1% in the control arm, prompting the authors to comment that the “use of a platinum/taxane in combination with radiation continues to gain acceptance based on its favorable toxic effects profile, ease of administration, and efficacy results.”

Mohan Suntharalingam et al also highlight the continuing debate over the role of surgery in oesophageal cancer patients.

“Given that consensus does not exist regarding the use of tri-modality therapy, this study included patients who were deemed to be medically unfit for surgery as well as those whose treating physicians supported a nonoperative approach”, they write, noting that 13% of trial participants later underwent surgery for residual or recurrent disease.

The authors remark that blood and tissue specimens were collected through the trial for analysis of biomarkers, such as p53 mutations, which have been linked to poor chemoradiation response, and KRAS mutations, which have been associated with EGFR inhibitor efficacy.

“The continued effort to identify populations of patients with molecular overexpression of potential targets will ultimately improve the ability to refine the treatment approach in this challenging disease”, they believe.


Suntharalingam M, Winter K, Ilson D, et al. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer. The NRG Oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 6 July 2017. doi:10.1001/jamaoncol.2017.1598

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