Highlights
- •In the PanaMa trial, the median overall DpR was 58.1% versus 54.9%, respectively.
- •Approximately 75% of the overall DpR was achieved during induction therapy.
- •Additional DpR achieved by maintenance therapy was numerically greater with Pmab.
- •DpR to induction was prognostic for PFS and OS of maintenance therapy.
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 (</≥) served as threshold.
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 trial information
NCT01991873.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: November 15, 2022
Accepted:
September 15,
2022
Received in revised form:
September 14,
2022
Received:
August 9,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
