Dr Su-Pin Choo of the National Cancer Centre in Singapore shares a BRAFV600E-mutant metastatic colorectal cancer (mCRC) patient case from her clinical practice and offers practical insights during a Q&A session at an industry-sponsored symposium.
Patient case: T4bN2bM1c BRAFV600E-mutant mCRC
A 54-year-old Chinese female with no notable past medical history presented with very severe abdominal pain of 4 days, which was associated with weight loss and loss of appetite. CT scan showed a right ovarian mass, an obstructing descending colon lesion, dilated large bowel loops, enlarged mesenteric nodes and peritoneal metastases. CA-125 level was elevated at 645 U/mL. She was diagnosed with T4bN2bM1c left-sided mismatch repair–proficient BRAFV600E-mutant mCRC. (Figure 1)
The patient underwent emergency sigmoid colectomy with bilateral salpingoophrectomy and required subsequent treatment.
Potential 1L options
“Doublet and triplet chemotherapy plus bevacizumab are both reasonable options,” said Choo. “Most of the time, we choose doublet chemotherapy plus bevacizumab, reserving triplet chemotherapy plus bevacizumab for younger patients with high-burden or right-sided disease.”
2L considerations
The global, randomized, phase III, multicentre, open-label BEACON trial demonstrated superiority of encorafenib (a BRAF inhibitor) plus cetuximab (an anti-EGFR monoclonal antibody) (EC; n=220) vs FOLFIRI plus cetuximab or irinotecan plus cetuximab (control; n=221) in patients with BRAFV600E-mutant CRC after progression on 1–2 prior regimens. Median overall survival (mOS) for EC vs control was 9.3 vs 5.9 months (hazard ratio [HR], 0.61; 95 percent confidence interval [CI], 0.48–0.77), while objective response rates (ORR) were 19.5 vs 1.8 percent. (Figure 2) [J Clin Oncol 2021;39:273-284]
“The main side effects [of EC] are diarrhoea, most of which is grade 1–2 [any grade, 38.4 percent vs 48.7 percent in control group], and [the rate of] grade ≥3 diarrhoea is only 2.8 percent [vs 10.4 percent in control group]. Arthralgia is very common and is also usually of low grade [any grade, 22.7 percent; grade ≥3, 1.4 percent], but it can be a bother to our patients, as well as headaches [any-grade, 19.9 percent; grade ≥3, 2.6 percent],” shared Choo. [J Clin Oncol 2021;39:273-284]
How was the patient treated?
“Because she had a very high burden of disease, you would want a high response rate,” said Choo. The patient received FOLFOXIRI plus bevacizumab in the first line (1L). Her ascites resolved, she had less bloating and improved appetite.
“After eight cycles, the patient progressed and was put on EC. She had partial response for about 8 months, which is longer than the mPFS of 4.3 months in the BEACON trial. The patient experienced grade 2 arthralgia, which required pain relief, and some skin dryness,” reported Choo. (Figure 3) [J Clin Oncol 2021;39:273-284]
Q&A highlights
Interchangeability of cetuximab with panitumumab
Choo noted that although cetuximab and panitumumab are from the same class, the data are more established for cetuximab. “The choice could be made according to patients’ experience of toxicity, as the two agents’ tolerability differs, with fewer allergic reactions yet more rash with panitumumab,” Choo suggested. “If there is a price difference, I would go for the cheaper drug. In my setting, there is no price difference, so I just follow the trial data, and I prefer using cetuximab.”
2L timing and monitoring
Choo advised moving on to second-line (2L) EC as soon as possible following progression on 1L treatment. “BRAFV600E patients do so badly, they crash rapidly, so I’m very vigilant about scanning, with a scan every 6 weeks, as per the trial. I want a quick indication of their response, because when they progress, they often go into visceral crisis, where nothing can be done. We also ask patients to tell us if there is an increase in pain or bloating, so we can do a scan right away, instead of waiting for the appointment, and change treatment if needed,” she said.