Chemotherapy re-challenge response rate in metastatic colorectal cancer.

Background: There are few treatment options in metastatic colorectal cancer (mCRC) after progression on standard chemotherapy. Third and fourth line therapies typically consist of regorafenib or trifluridine-tipiracil, however, clinical benefit of these medications is limited, as progression free survival is approximately 1.9 months for regorafenib (Grothey et al. 2013) and 2.0 months for trifluridine-tipiracil (Mayer et al. 2015). Another choice in this setting may include the re-initiation of previously used chemotherapy, therefore in this study we assessed the efficacy and tolerability of chemotherapy re-challenge.

Methods: This was a retrospective, cohort study assessing patients with mCRC who were 18-89 years of age and treated with re-challenge chemotherapy. Re-challenge chemotherapy was defined as re-initiation of oxaliplatin or irinotecan-based regimens at least nine months from the end of initial exposure. A minimum of four chemotherapy cycles was required to qualify as initial exposure. The key endpoints of this study were clinical benefit rate (CBR), defined as the proportion of patients with partial response or stable disease, and time to progression (TTP).

Results: A total of 67 chemotherapy re-challenges were accounted for in 51 patients. The overall CBR was 70.7%. Partial responses occurred in 50.7% cases. The TTP was 6.0 months. For the 51 cases of first re-challenge, the CBR was 75.5% and TTP was 6.5 months. Fourteen patients had a second re-challenge, and in these patients, the CBR was 61.5% and TTP was 4.1 months.

Conclusions: Oxaliplatin or irinotecan-based re-challenge should be considered as a third or fourth line treatment option in select patients with mCRC. CBR and especially TTP compare favorably to approved third line therapies such as regorafenib or trifluridine-tipiracil.