Real-World Treatment Patterns Among Patients With HER2-Amplified Metastatic Colorectal Cancer

John Strickler, MD, Duke Cancer Center, Duke Health, presents findings from his clinical‑genomic database study on real‑world treatment patterns in patients with HER2‑positive metastatic colorectal cancer (CRC) in the US, analyzing how treatment patterns changed before 2018 and after 2018.

Transcript: On behalf of my co‑authors, I'm pleased to present our poster, "Characteristics and Treatment Patterns Among Patients With HER2‑Amplified Advanced/Metastatic Colorectal Cancer". This is a clinical‑genomic database study.

As some background, HER2 gene amplification is present in approximately 3% of patients with metastatic colorectal cancer. It's only been in recent years that we've identified HER2 as an important target in metastatic colorectal cancer.

That has followed some key publications and the subsequent inclusion of HER2‑directed therapies in the NCCN Treatment Guidelines, which occurred in 2019. In the NCCN Guidelines, testing of HER2 amplification is recommended for patients with metastatic colorectal cancer.

Despite the fact that more clinicians are aware of HER2 as a target for metastatic colorectal cancer, and there are some therapies listed in the NCCN Guidelines, there are currently no FDA‑approved therapies for these patients, and we have very limited real‑world data on practice patterns around these patients with HER2‑positive metastatic colorectal cancer.

In this poster, we present real‑world treatment patterns in patients with HER2‑positive metastatic colorectal cancer specifically in the United States, and we look at how treatment patterns change before 2018 and after 2018.

A brief word on the methods, patients were identified from the Guardant INFORM clinical‑genomic database, which captured patients between January 2014 and September 2020. This database includes aggregated US commercial payer claims with the Guardant360 genomic testing results.

Key criteria of the study include ERBB2, or HER2, amplification from the Guardant360 test, at least one inpatient or two outpatient claims with a colorectal cancer diagnosis code, and three months or more follow‑up from the index date.

The index date is important. That was defined as the date of the first Guardant report with HER2 amplification or the start date of a HER2‑directed regimen, whichever was earlier. Treatment patterns, including first treatment received post‑index and real‑world time to next treatment, were assessed for patients receiving approved systemic cancer therapy post‑index.

Some background on the results, there were 142 patients included in the study population. 19.7% of patients also had a KRAS mutation in addition to HER2 amplification, and the HER2 plasma copy median number was 2.9. We found some interesting aspects to the treatment patterns.

In the overall cohort, anti‑VEGF treatment plus or minus chemotherapy were given to 30% of patients, and HER2‑directed therapies were given to just under 30% of patients. Those were the two most commonly received regimens.

For patients with an index date before 2018, anti‑VEGF therapy with chemotherapy was the most common regimen, whereas after the index post‑date, HER2‑directed regimens were more common, showing that there was a shift in treatment patterns towards HER2‑directed therapies after 2018.

Also of note, use of anti‑EGFR therapies declined from 12.7% before 2018 to 6.3% after 2018. We did see decreased use of anti‑EGFR therapies, as HER2 amplification is thought to drive resistance to that class of therapies.

In the overall cohort, the median time to next treatment was 8.4 months. What we found is that patients treated with HER2‑directed therapy had numerically longer median time to next treatment compared with those treated with non–HER2‑directed therapies.

It was 11.6 months for the HER2‑directed therapies versus 7 months for non–HER2 therapies. Although that was not statistically significant, it did show a potential improved outcome with those HER2‑directed therapies.

In conclusion, using this clinical‑genomic dataset, this study highlights some significant unmet need among patients with HER2‑positive metastatic colorectal cancer. We observed heterogeneous treatment patterns among patients, suggesting a lack of standard of care.

Despite increased awareness and increased use of HER2‑directed therapies after 2018, still, the utilization of these therapies was low. Approximately 10% of patients received anti‑EGFR‑based regimens despite the fact that HER2 is thought to drive resistance to that class of therapies.

In closing, we'd like to make the point that effective therapies and enhanced awareness of this unmet need in this population will facilitate improved targeted treatment strategies.