Tweet Chat Recap: Kasi Examines an Unresectable Colorectal Cancer Case

Targeted Oncology was joined on Twitter by Pashtoon M. Kasi, MD, MD, MBBS, MS, oncologist and researcher at Weill Cornell Medicine and New York-Presbyterian Hospital, for the discussion of a 50-year-old woman with recently diagnosed, unresectable colorectal cancer.

Within the scenario, the otherwise healthy woman received a biopsy after having her first routine colonoscopy due to a suspicious mass in the ascending colon. The patient had T3N2 disease and received six months of adjuvant capecitabine, oxaliplatin (CAPEOX). About a year after she received the diagnosis, a CT of her abdomen, pelvis and chest showed multiple small bilateral liver nodules which were 5mm or less.

Additionally, the patient had an ECOG performance status of 0 and when molecular testing was done, the tissue biopsy showed her disease to be KRAS/ BRAF wild-type, microsatellite stable, HER2-negative and NTRK alteration negative.

During the tweet chat, Kasi discussed his major concerns for this patient in regards to multiple views.

“My concerns from an efficacy standpoint [is] worse biology [and] from a quality-of-life standpoint, [I would] be careful of cumulative neuropathy. Don’t overuse oxaliplatin in palliative intent setting. Consider maintenance after 4-6 cycles,” said Kasi.

There are various chemotherapy regimens oncologists can choose from when determining the best fit for a patient with colorectal cancer. In a Twitter poll ahead of the discussion, Targeted Oncology followers shared their thoughts on what chemotherapy regimen they would be most likely to recommend to this specific patient? The majority of followers (36%) voted for the FOLFOXIRI, while other followers (29%) voted for FOLFOX and FOLFIRI (21%). Additionally, some people voted for other (14%).

Kasi noted the interesting distribution on chemotherapy options and triplet versus doublet options during the tweet chat. It is important to individualize each case and personalize treatments for each patient, and Kasi expresses the underutilization of triplets currently in this field.

“I don’t think the answer is black and white; but I’ve have been using more triplets. For any recurrent/ metastatic unresectable patient with colorectal cancer, I’d consider and enroll in the SOLARIS clinical trial [NCT04094688],” said Kasi in the tweet chat. “Prior cumulative neuropathy on oxiplatin affects choice. More difficult if they already have neuropathy, especially if they got 6 months of chemotherapy. [It is] important to be able to quantify cumulative exposure/ residual side effects.”

In regard to upfront therapy, Kasi explained that some of the options outside of clinical trials is a type of doublet or triplet chemotherapy paired with biologics including VEGF or EGFR inhibitors.

Additionally, if trial is not an option, the treatment option that Kasi would recommend to a patient in his practice based on this case would be to use a triplet option as they are “underutilized.”

Based on various data from 5 analyses of studies using triplets including, CHARTA (NCT01321957), OLIVIA (NCT00778102), STEAM (NCT01765582), TRIBE (NCT00719797), and TRIBE2 (NCT02339116), Kasi explains he would most likely choose the triplet plus bevacizumab (Avastin) regimen examined in TRIBE.

The randomized, phase 3 TRIBE trial compared 2 combination chemotherapy regiments given together with bevacizumab to see how well they work as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

The trial randomly assigned 508 patients 1:1 to receive FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Bevacizumab was given as a 5 mg/kg intravenous (IV) dose. FOLFIRI consisted of a 180 mg/m2 IV infusion of irinotecan for 60 min followed by a 200 mg/m2 intravenous infusion of leucovorin for 120 min, a 400 mg/m2 IV of fluorouracil, and a 2400 mg/m2 continuous infusion of fluorouracil for 46 hours.

FOLFOXIRI consisted of a 165 mg/m2 IV infusion of irinotecan for 60 min, followed by an 85 mg/m2 IV infusion of oxaliplatin given concurrently with 200 mg/m2 leucovorin for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 hours.

Findings from the trial showed that at a median follow-up of 48.1 months, the median overall survival (OS) in the FOLFOXIRI plus bevacizumab group was 29.8 months (95% CI, 26.0 - 34.3) compared with 25.8 months (22.5 - 29.1) in the FOLFIRI plus bevacizumab group (HR, 0.80; 95% CI, 0.65 - 0.98; P =.03).

Median OS was reported as 37.1 months (95% CI, 29.7 - 42.7) in the RAS and BRAF wild-type subgroup compared with 25.6 months (22.4 - 28.6) in the RAS-mutation-positive subgroup (HR 1·49, 95% CI, 1.11 - 1.99) and 13·4 months (8.2 - 24.1) in the BRAF-mutation-positive subgroup (HR, 2.79; 95% CI, 1.75 - 4.46).

Kasi concluded the tweet chat by discussing what factors would influence an oncologist’s decision of treatment selection for this patient. He shared that it is a “joint or shared-decision,” and that tumor related factors including RAS/RAF status, MMR/MSI status and sidedness are just as important as patient-related factors including performance status and patient preference. 

“More is not always better. Forty-five is the new 50 for screening for average risk individuals, sooner if risk factors. Get screened,” Kasi said.

REFERENCES:

1. Li J, Qin S, Xu RH, et al. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855
2. Cremolini C, Antoniotti C, Stein A, et al. Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus bevacizumab as initial therapy of unresectable metastatic colorectal cancer. J Clin Oncol. 2020;JCO2001225. doi:10.1200/JCO.20.01225