Autumn J McRee, MD, associate professor of medicine, The University of North Carolina at Chapel Hill, presented on three clinical studies of targeted therapies in unique niches of metastatic colorectal cancer.
The presentation was given at the American Society of Clinical Oncology (ASCO) Annual Meeting (May 30, 2020).
The first study Dr McRee showcased was the DESTINY-CRC01 study – a phase II, multicenter, open-label study of an antibody drug conjugate (T-DXd) in patients with HER2-expressing disease. Patients in the study had unresectable or metastatic disease, had received at least two prior lines of therapy, and were RAS/BRAF wildtype. Patients were divided into three cohorts, the first of which included 53 patients who were HER2-positive (IHC 3+ or IHC 2+/ISH+) and treated with T-DXd (6.4 mg/kg). The primary endpoint of DESTINY-CRC01 was confirmed ORR in this cohort.
ORR was recorded as 45.3% in the experimental cohort, and there seemed to be an improvement regardless of prior HER2 treatment. Dr McRee posed the question of whether a HER2-specific approach is superior to standard-of-care options in the refractory setting, to which she noted that adding T-DXd to the treatment paradigm offers an improvement in progression-free survival (PFS) as well as higher response rates.
“Without a doubt this trial is clinically relevant,” she said, adding that testing for HER2 amplification should be considered standard of care in colorectal cancer. Nonetheless, questions still remain about sequencing HER2-targeted therapies and whether to treat patients with RAS mutations.
Next, Dr McRee discussed the updated survival results from the BEACON trial – a randomized, three-arm, phase III study. Patients with BRAF V600E-mutated metastatic disease with progression after at least one prior regimen received encorafenib plus binimetinib and cetuximab (Arm A; n = 205); encorafenib plus cetuximab (Arm B; n = 205); or FOLFIRI plus cetuximab, or irinotecan plus cetuximab (Control Arm; n = 205). The primary endpoint of the study was overall survival (OS) of Arm A vs Control Arm.
Updated survival curves showed identical median OS for Arm A and Arm B (9.3 months) compared with that of Control Arm (5.9 months). Response rates were also higher in Arm A and Arm B compared with Control Arm, she noted.
“This trial shows how our poorest prognostic group in colorectal cancer now has viable options,” Dr McRee stated, and is “immediately practice-changing, given the FDA approval of encorafenib and cetuximab.” The results of the ANCHOR-CRC study will help understand if this targeted approach can be used in earlier lines of therapy.
The third study to be presented was the PANDA study – a non-comparative randomized clinical trial of older patients (median age, 77 years) with RAS/RAF wildtype metastatic disease. Patients received either FOLFOX plus panitumumab (Arm A) for up to 12 cycles followed by panitumumab maintenance or 5FU/LV plus panitumumab (Arm B) for up to 12 cycles followed by panitumumab maintenance. The primary objective of the study was PFS of each arm compared with a literature-based historic control of less than or equal to 6 months.
The PFS endpoint was met in both arms of the study, Dr McRee stated; the median PFS was 9.6 in Arm A and 9.1 in Arm B. Both arms had promising response rates of greater than 50%, she added.
In her concluding remarks on the PANDA study, Dr McRee mentioned that the study may be clinically relevant and has the potential to be practice-changing. While encouraging response rates were observed in the first-line setting in both treatment arms, further overall survival and geriatric assessment data are needed.—Zachary Bessette
