Patterns of progression, treatment of progressive disease and post-progression 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=48, CT and CTX n=61) patients with progressive disease at the cut-off 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=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.

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial

“…Further interrogation of the progression events in the New EPOC population has revealed some informative observations. 25 First, additional data collected after the interim analysis showed that there were numerically more multisite progressions in the chemotherapy plus cetuximab group than in the chemotherapy alone group. Second, this updated analysis shows post-progression survival to be shorter for the chemotherapy plus cetuximab group.…”

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer

“…S4b ). Post-progression survival (PPS) is defined as the time from date of progression to death [ 38 ]. We analyzed the effects of five candidate TFs on OS, PFS, and PPS by using the website tool Kaplan–Meier Plotter [ 36 ].…”

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches

“…Another systematic review concluded that combination regimens increased cancer response and resectability rates in case of unresectable CRLM, while studies on NACHT failed to definitely prove a survival benefit for resectable tumours, with enhanced risks of perioperative complications[ 90 ]. In the new EPOC RCT[ 94 ], the addition of cetuximab to perioperative systemic FOLFOX CHT of KRAS exon 2 wild-type resectable or suboptimally resectable CRLMs resulted in unexpected shorter progression-free survival rates than systemic CHT alone; these disappointing results were related to disease progression consistent with failure of systemic micrometastatic disease control[ 95 ] and have been confirmed in the updated analysis of this study[ 96 ], where patients in the cetuximab group experienced significantly worse OS rates. Recent retrospective series do not support the use of NACHT in upfront resectable CRLM.…”