Depth of response of induction therapy and consecutive maintenance treatment in patients with RAS wild-type metastatic colorectal cancer: An analysis of the PanaMa trial (AIO KRK 0212).
By: Greta Sommerhäuser, Annika Kurreck, Alexander Beck, Uli Fehrenbach, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Mueller, Alexander O Koenig, Ludwig F V Weikersthal, Eray Goekkurt, Siegfried Haas, Arndt Stahler, Volker Heinemann, Swantje Held, Annabel H S Alig, Stefan Kasper, Sebastian Stintzing, Tanja Trarbach, Dominik P Modest

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Berlin, Germany.
2022-08-09; doi: 10.1016/j.ejca.2022.09.011
Abstract

Background

In patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin [FU/FA], oxaliplatin [FOLFOX] and panitumumab [Pmab]) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial.

Methods

Central radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (

Results

Out of 248 patients receiving maintenance therapy, 211 were evaluable for DpR analyses (FU/FA + Pmab, n = 106; FU/FA alone, n = 105). The overall DpR in all patients was 56.5%. DpR of induction therapy (42.5%) accounted for the largest proportion (75.2%) of the overall DpR. While greater DpR to induction therapy was significantly associated with prolonged PFS (HR 0.70, 95% CI 0.52-0.93, p = 0.013) and OS (HR 0.38, 95% CI 0.28-0.51, p < 0.001), there was no significant correlation of DpR and maintenance treatment arm.

Conclusions

In the PanaMa trial, the overall DpR was similar to DpR achieved by other epidermal growth factor receptor-based regimens. DpR to induction therapy accounted for three quarters of the total tumour shrinkage potentially suggesting that FOLFOX plus Pmab can be de-escalated following induction without substantially compromising efficacy. DpR to induction therapy was prognostic but not predictive for efficacy of consecutive maintenance therapy.

Clinical

NCT01991873.



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PMID:36399909






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