Patterns of progression, treatment of progressive disease, and postprogression survival in the new EPOC study.

Abstract

Background: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. Methods: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n ¼ 48, CT and CTX n ¼ 61) patients with progressive disease at the cutoff date for analysis of November 2012. Results: The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P ¼ 0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. Conclusions: Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

Cetuximab Is Contraindicated in the Perioperative Treatment of Colorectal Liver Metastases

“…4 This supports the contention that inadequate surgery was not responsible for the shorter progression-free survival that was observed in the group that received chemotherapy with cetuximab. In fact, the pattern of disease progression is much the same in the group treated with cetuximab and chemotherapy and the group treated with chemotherapy alone; approximately half of all progression events involved the liver only in both groups (chemotherapy alone group, 52%; chemotherapy plus cetuximab group, 48%).…”

Why post‐progression survival and post‐relapse survival are not appropriate measures of efficacy in cancer randomized clinical trials

“…For example, a phase III trial evaluating the addition of cetuximab to perioperative chemotherapy for the treatment of potentially operable colorectal liver metastases, reported both a shorter PFS and a shorter PPS for the experimental arm. Here a shorter PPS indicates a detrimental effect of the experimental treatment …”

“…Post‐relapse survival (PRS)―time from relapse to death―or post‐progression survival (PPS)―time from progression to death―is another outcome that has been reported in clinical trials and observational studies as a complement to overall survival and, occasionally, as the main result . Several pooled analyses of trials have studied the correlation of PRS/PPS, also referred to as “post‐disease‐free survival” and “treatment failure survival,” with PFS and overall survival …”