How Comprehensive Molecular Testing and Evolving Therapies Shaped a 50-Year-Old Woman’s Path to Hope

A 50-year-old Caucasian woman with a history of asthma began experiencing debilitating radicular and low back pain. Imaging soon revealed large lesions in the sacrum (spreading into the spinal canal) and a suspicious lung nodule in the right middle lobe. Additional scans confirmed multiple liver metastases. A biopsy of her liver lesion revealed a moderately differentiated adenocarcinoma consistent with a colorectal primary. Colonoscopy pinpointed a near-circumferential rectosigmoid mass.

Her family history of malignancies—ranging from ovarian cancer in her mother to adenoid cystic salivary gland cancer in her sister—raised early concern about potential hereditary syndromes. Nevertheless, immuno-histochemical testing indicated her tumor was microsatellite-stable (MSS), ruling out a mismatch repair deficiency.

She first received palliative radiation (30 Gy in 10 fractions) for symptomatic control of sacral and iliac metastases. Subsequently, first-line mFOLFOX-6 chemotherapy combined with bevacizumab achieved a partial response—yet eventual rectal bleeding prompted discontinuation of bevacizumab. Disease progression led to second-line FOLFIRI chemotherapy, which offered temporary stability. Bevacizumab was reintroduced, providing an additional six months of disease control before another progression event. At this point, her carcinoembryonic antigen (CEA) had risen from 15.8 to 69.6 mcg/L.

In search of new options, the team replaced bevacizumab with panitumumab alongside FOLFIRI. A notable partial response followed, with up to 36% tumor shrinkage observed by RECIST criteria and stable disease for eight months. Crucially, next-generation sequencing later revealed a non-canonical KRAS p.A59T mutation (undetected by initial Sanger sequencing of exon 2)—reinforcing the importance of comprehensive molecular testing.

After disease progression, she moved to third-line regorafenib at a reduced dose, but progression soon followed. Finally, she enrolled in a phase I clinical trial combining a histone deacetylase inhibitor and a PD-L1 inhibitor, demonstrating the ever-evolving nature of metastatic colorectal cancer treatment strategies.