Conference Coverage

Worse survival with cetuximab plus chemo for CRC liver mets

 

Key clinical point: Patients with resectable colorectal liver metastases (CRLM) fared worse when cetuximab was added to neoadjuvant and adjuvant chemotherapy.

Major finding: Median overall survival was 81 months for patients assigned to chemotherapy alone, vs. 55.4 months for patients assigned to chemotherapy plus cetuximab.

Data source: Mature analysis of a randomized phase 3 trial in 257 patients with resectable CRLM. The trial was halted for futility in 2012.

Disclosures: Cancer Research UK supported the study. Dr. Bridgewater disclosed honoraria and speakers fees from Merck, Celgene, and Servier, and travel support from Amgen, Merck Sharpe Dohme, and Servier.


 

AT ESMO 2017

– Adding cetuximab (Erbitux) to chemotherapy before or after surgery for resectable colorectal liver metastases resulted in significantly worse survival compared with perioperative chemotherapy alone, mature results of the randomized New EPOC trial confirmed.

Among 257 patients with KRAS exon 2 wild-type resectable colorectal liver metastases (CRLM) or suboptimally resectable CRLM, median overall survival (OS) was 81 months for patients assigned to neoadjuvant and adjuvant chemotherapy alone, compared with 55.4 months for patients who received perioperative chemotherapy plus cetuximab, reported John Bridgewater, MD, of University College London Cancer Institute.

Dr. John Bridgewater, University College London Cancer Institute
Dr. John Bridgewater
Postprogression survival (PPS) was “particularly poor” for patients assigned to cetuximab, the investigators noted in a poster presented at the European Society for Medical Oncology Congress.

Median progression-free survival (PFS) was 22.2 months without cetuximab, vs. 15.5 months with chemotherapy plus cetuximab, a difference that was not statistically significant. However, when the primary analysis of the trial was reported in 2014 in The Lancet: Oncology, cetuximab was associated with significantly shorter PFS. The trial was halted in 2012 on the recommendation of the data monitoring committee.

“In the context of perioperative therapy for resectable CRLM, chemotherapy plus cetuximab confers a shorter OS and PPS,” Dr. Bridgewater and his associates wrote.”This is primarily in those with conventionally favorable prognostic features suggesting that cetuximab induces adverse biology in some patients, whose biomarker profile is ongoing.”

They also found that there were no differences in overall survival among patients with responses to chemotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) and those who did not have responses, “suggesting that in this predominantly operable population, any conferred benefit of systemic treatment is through elimination of micro-metastatic disease rather than by downsizing of radiologically evaluable disease.

The randomized phase 3 Medical Research Council COIN trial, results of which were reported at the 2010 annual meeting of the American Society of Clinical Oncology and later published in The Lancet, failed to show a benefit for the addition of cetuximab to front-line oxaliplatin-based chemotherapy for metastatic CRC. Median OS in KRAS wild-type patients was 17 months when cetuximab was added to chemotherapy with oxaliplatin and an intravenous or oral fluoropyrimidine, compared with 17.9 months when chemotherapy was delivered without cetuximab. Median PFS held at 8.6 months in both arms of the trial.

The New EPOC investigators described their study as a “natural extension” of the COIN study as well as earlier trials and phase 2 studies of neoadjuvant and adjuvant therapy in this patient population.

From 2007 through 2012, 257 patients were randomly assigned to receive chemotherapy alone, or chemotherapy with rituximab. Chemotherapy consisted of one of two regimens: oxaliplatin 85 mg/m2 intravenously over 2 hours and fluorouracil bolus 400 mg/m2 intravenously over 5 minutes followed by a 46-hour infusion of fluorouracil 2,400 mg/m2 repeated every 2 weeks; or oxaliplatin 130 mg/m2 intravenously over 2 hours and oral capecitabine (Xeloda) 1,000 mg/m2 twice daily on days 1-14 repeated every 3 weeks.

After a median follow-up of 69 months, there were 130 deaths from any cause. As noted before, median OS was significantly shorter with cetuximab. The hazard ratio for death with cetuximab was 1.45 (P = .035). Median PFS did not differ in this most recent analysis, however.

Median PPS was 35.4 months for chemotherapy alone, compared with 23.5 months for chemotherapy plus cetuximab (P = .014).

The poor overall survival and PFS results indicate that “cetuximab cannot be recommended for perioperative treatment in patients with resectable disease,” said Thomas Gruenberger, MD, an oncologic surgeon at Rudolf Hospital in Vienna, who was invited to review the results in a poster discussion session.

Cancer Research UK supported the study. Dr. Bridgewater disclosed honoraria and speakers fees from Merck, Celgene, and Servier, and travel support from Amgen, Merck Sharpe Dohme, and Servier.

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