Experts on colorectal cancer present the case of a 40-year-old woman with CRC, who receives later-line treatment with trastuzumab deruxtecan, and share their initial thoughts.
Cathy Eng, MD, FACP, FASCO: I’m going to trouble you again, and have you present case number 3. Which is a patient with HER2-positive metastatic colorectal carcinoma who receives treatment with trastuzumab deruxtecan.
Arvind Dasari, MD, MS: This is another young patient, 40 years old, who presented with hematochezia and left lower quadrant abdominal discomfort. On imaging she was noted to have a low sigmoid colon mass with regional lymph nodes and no other metastatic disease. She had a follow-up colonoscopy that revealed a nonobstructive distal sigmoid colon mass and a biopsy confirmed poorly differentiated adenocarcinoma. She underwent low anterior resection, and pathology revealed a microsatellite stable tumor with moderately to poorly differentiated adenocarcinoma. This was staged pT4aN1b with full penetration of the visceral peritoneum. Three out of 17 lymph nodes being involved along with lymphovascular and perineural invasion.
Given this advanced stage, the patient was started on adjuvant FOLFOX [leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin] chemotherapy, but unfortunately she had an infusion reaction to oxaliplatin midway through and adjuvant therapy was completed with single agent 5FU [fluorouracil] to complete 6 months of therapy. She was on surveillance after about 2 years or so, and was noted to have an isolated lung lesion that was resected. After discussion, she received adjuvant capecitabine additionally for another 6 months. Unfortunately, around 18 months later, she had multiple bilateral lung mets [metastases], and additional molecular profiling done at that time showed that the tumor was RAS wild-type, BRAF wild-type, and HER2 3+ on IHC [immunohistochemistry] and confirmed on NGS [next-generation sequencing].
She was treated with FOLFIRI [folinic acid, fluorouracil, and irinotecan] plus bevacizumab for about 8 months with continued progression. Her care predated the results of the MOUNTAINEER trial (NCT03043313). She was subsequently started on trastuzumab plus pertuzumab. The first scan after starting this therapy showed a response. Then she continued this therapy. On the next restaging, what we saw was that the previously noted lesions were all responding really nicely. That’s on the left panel. But she was noted to have a couple of new lesions that were not previously noted. We got a follow-up PET [positron emission tomography] scan that confirmed these new lesions, including a rib met [metastasis] that perhaps could have been seeding when a prior lung met [metastasis] was resected and an adrenal lesion as well.
Her case was discussed in a multidisciplinary conference and the recommendation was to perhaps discontinue the current therapy and consider radiation to these escape lesions if there was no other progressive disease on the next scan. Indeed, she did not have any other progressive disease. She received ablative doses of radiation to this adrenal met [metastasis] and the rib met [metastasis] and continued trastuzumab and pertuzumab for an additional 9 months before she had progressive disease. She then started on fam-trastuzumab, subsequently. The complications that she had on this were grade 2 neutropenia, otherwise asymptomatic times 2 requiring dose reduction, and had clinical benefit with stable disease and continues to do well on this therapy currently.
Cathy Eng, MD, FACP, FASCO: Thank you so much. Dr Parikh, this is a young woman, she had FOLFOX and then had a reaction to oxaliplatin. She was prescribed FOLFIRI and then got pertuzumab. What are your next steps for a patient such as this that shows up in your clinic?
Aparna Parikh, MD: This is such a provocative case on so many levels, so many things to discuss. But I think the management is exactly up to date with what I would have done. I think it’s really smart with being mindful of all sites of progression too when you’re on targeted therapies and not putting the targeted therapy on the back burner as you did by going ahead and giving ablative doses of radiation. That patient was able to regain response again for another 9 months. I think that’s an important teaching point from this case that even with mixed responses, you can still go after potentially progressive sites and still derive benefits. Just with new sites, metastases don’t necessarily give up your targeted therapy too early. Then beyond that, I think it’s a rapidly evolving landscape in terms of what we’re going to be doing post initial HER2-directed therapy.
Transcript edited for clarity.