COLOXIS is an interesting computer-based learning model that seems to be able to predict which patients are likely to benefit from adjuvant chemotherapy in colorectal cancer. This, along with ctDNA tests, may change whom we choose to offer adjuvant chemotherapy.
A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects.
We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS– (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect.
Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS–. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS– patients did not (COLOXIS– HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65).
The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.
Epi and nivo for mismatch repair-deficient (dMMR) colon cancer had 98% response rate with 68% complete response, non-recurred with a median of follow up of 26 months. Does this mean bye-bye surgery??? Probably. We will need to assess those who have complete response and have a close follow up. CtDNA may play big role here, along with a need for randomized trials.
Negative study for the use of HIPEC in the adjuvant setting of high-risk or locally advanced colorectal cancers, including those with perforation and peritoneal invasion. HIPEC doesn’t seem to reduce the risk of peritoneal recurrence after potentially curative resection.
Stopping oxaliplatinum and cont. of 5FU is better than stopping all chemotherapy. An option for patients with worsening neuropathy or other oxaliplatinum toxicity.
Get your patients moving, even in the adjuvant setting! Of course, a lot of bias is possible here, but there was nearly a 10% difference in cure at three years.
Excellent study demonstrating the value of evaluation of ctDNA/molecular disease and impact of adjuvant chemotherapy. Guidelines will change rather significantly (for different cancers) in this decade, as to who actually needs post-operative chemotherapy. More prolonged follow-up is warranted.
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