Maintenance Therapy After Oxaliplatin Discontinuation Based on Panitumumab
Panitumumab is an approved therapy for metastatic colorectal cancer without RAS oncogene mutation (wtRAS mCRC) and has been evaluated for 1st-line treatment through randomized phase II (PEAK) and III (PRIME) studies. A retrospective analysis of these studies assessed the efficacy and safety of panitumumab as the basis for therapy in these patients after discontinuation/termination of oxaliplatin.
Maintenance Therapy Strategy
Data from clinical trials show that first-line therapy administration until disease progression pertains to only a subpopulation of mCRC patients; for most, systemic therapy is de-escalated before progression. Guidelines for subsequent maintenance therapy administration are especially important for regimens involving agents like oxaliplatin, which is associated with cumulative neurotoxicity. This can necessitate the interruption/termination of treatment even in patients otherwise responding well. Effective and acceptably safe strategies in these cases include stop-go and/or maintenance therapy.
The role of anti-EGFR antibodies in maintenance therapy is relatively underexplored, and thus panitumumab in maintenance therapy after oxaliplatin discontinuation has not been thoroughly evaluated by clinical trials.
Analysis Objectives
In the PRIME study, the first-line regimen was FOLFOX4 ± panitumumab, and in the PEAK study, it comprised mFOLFOX6 + panitumumab or mFOLFOX6 + bevacizumab. Monitored parameters included median progression-free survival (PFS) and overall survival (OS) from randomization (PFSR, OSR) and from oxaliplatin discontinuation (PFSOX, OSOX), as well as toxicity. The results of the different types of maintenance therapy were not compared through statistical analysis.
Findings
The median duration of maintenance panitumumab (P) plus 5‐fluorouracil/leucovorin (5‐FU/LV) treatment was 21 weeks (interquartile range: 11−41 weeks). In the case of 5‐FU/LV ± bevacizumab (B), it was 16 (6−31) weeks. The treatment outcomes achieved using both methods are summarized in the table below. The most commonly reported adverse events included rash, fatigue, and diarrhea.
|
Parameter |
Treatment |
PRIME months: median (95% confidence interval) |
PEAK months: median (95% confidence interval) |
|
OSR |
5-FU/LV + P |
40.2 (30.3−50.4) |
39.1 (34.2−63.0) |
|
5-FU/LV ± B |
24.1 (17.7−33.0) |
28.9 (21.0−32.0) |
|
|
PFSR |
5-FU/LV + P |
16.6 (11.3−23.6) |
15.4 (11.6−18.4) |
|
5-FU/LV ± B |
12.6 (9.4−16.2) |
13.1 (9.5−16.6) |
|
|
OSOX |
5-FU/LV + P |
33.9 (24.7−42.8) |
33.5 (24.5−54.9) |
|
5-FU/LV ± B |
16.4 (12.4−24.1) |
23.3 (15.7−26.3) |
|
|
PFSOX |
5-FU/LV + P |
11.7 (7.8−19.2) |
9.7 (5.8−14.8) |
|
5-FU/LV ± B |
7.1 (5.6−10.2) |
7.0 (3.9−10.6) |
Conclusion
Maintenance therapy with panitumumab plus 5‐FU/LV after the discontinuation/termination of oxaliplatin was well tolerated and may be an acceptable therapeutic option for patients who respond well to first-line therapy. These findings need to be supplemented and confirmed by insights from prospective studies.
(mir)
Source: Modest D. P., Rivera F., Bachet J. B. et al. Panitumumab-based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: a retrospective analysis of two randomized trials. Int J Cancer 2019; 145 (2): 576–585, doi: 10.1002/ijc.32110.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
