How Do We Optimally Use Cetuximab for Metastatic CRC?
How Do We Optimally Use Cetuximab for Metastatic CRC?
With the addition of the NORDIC VII Phase III results to the data described above and in Table 1, we can now conclude the following:
We would add that overall there is little doubt that cetuximab has a clear role in the first-line setting of metastatic CRC, but the timing and context of its use has assumed increasing importance.
In summary, the case for cetuximab administration in combination with irinotecan-based 5FU doublets has largely been made by a progressively less compelling body of evidence for its use with oxaliplatin-based chemotherapy, something that, in the authors' opinion, should inform our current clinical practice.
Conclusion
With the addition of the NORDIC VII Phase III results to the data described above and in Table 1, we can now conclude the following:
Definitive evidence for first-line cetuximab use in the metastatic CRC setting is only offered by the CRYSTAL study, which looks at its combination with irinotecan-based 5FU regimens. There is also a clear advantage with cetuximab use in Ras wild-type patients in this trial;
Despite initial reports to the contrary (OPUS study), up-to-date trial evidence suggests that there may be an interaction between cetuximab and oxaliplatin that interferes with their potential efficacy (COIN and NORDIC VII studies), although it has been suggested that an interaction may occur between cetuximab and capecitabine (COIN study). For patients where the use of irinotecan-based chemotherapy is contraindicated, the PRIME trial offers the most robust Phase III evidence for the combination of oxaliplatin with an EGFR inhibitor in the first-line setting: panitumumab added to FOLFOX4 significantly extended PFS from 8 to 9.6 months;
Unlike with irinotecan-based regimens in the CRYSTAL study, current trial evidence does not fully corroborate initial suggestions that cetuximab use with oxaliplatin-based regimens is only relevant to patients with Ras wild-type cancers (COIN and NORDIC VII studies). It should be noted, however, that this is not the case with panitumumab, where benefits in the PRIME study were exclusively ascribed to patients with Ras wild-type cancers;
RR (and perhaps PFS), often used as a primary end point in Phase II trials, is not a useful surrogate marker for outcome when assessing cetuximab in this setting (OPUS and CELIM studies).
We would add that overall there is little doubt that cetuximab has a clear role in the first-line setting of metastatic CRC, but the timing and context of its use has assumed increasing importance.
In summary, the case for cetuximab administration in combination with irinotecan-based 5FU doublets has largely been made by a progressively less compelling body of evidence for its use with oxaliplatin-based chemotherapy, something that, in the authors' opinion, should inform our current clinical practice.
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