Testing for HER2 in patients with colorectal cancer (CRC) should become a new standard of care, say experts discussing new results from a phase 2 trial showing benefit with trastuzumab deruxtecan (T-DXd, marketed as Enhertu, AstraZeneca/Daiichi Sankyo).
This drug is approved in the United States for use in the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have already received two or more prior anti–HER2-based regimens in the metastatic setting.
Results come from a phase 2 study, dubbed DESTINY-CRC01, in patients with previously treated HER2+ advanced CRC.
The results show that, in patients with the highest degree of HER2 positivity, T-DXd was associated with an objective response rate of over 45% and a median progression-free survival (PFS) of almost 7 months.
They “demonstrate, in our opinion, the potential of T-DXd as a treatment option” for patients with advanced HER2-positive colorectal cancer that is refractory to standard therapies, said lead investigator Salvatore Siena, MD, from Niguarda Cancer Center, in Milan, Italy.
He presented the results at the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because of the coronavirus pandemic.
At the same time, results from another study, this time in gastric cancer patients, were published online in the New England Journal of Medicine.
Interstitial lung disease as adverse event
The safety profile of T-DXd seen in the colorectal trial “is consistent with what has been previously reported,” said Siena, adding that most of the adverse events were low grade. But he noted there was also a serious adverse effect – interstitial lung disease (ILD). This occurred in 6% of patients, two of whom died. This is “an important risk and requires careful monitoring and proper intervention,” he emphasized.
The ILD adverse effect in this study is “a concern…and something to consider,” commented discussant for the study Michael S. Lee, MD, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. But he added that these are the “the best data so far for subsequent anti-HER2 therapy in colorectal cancer”.
Also, the dose of drug used in this trial was higher than that approved for breast cancer, and the incidence of ILD “begs the question of whether we should be using a lower dose in this patient population,” said Autumn J. McRee, MD, also from Lineberger, in a highlights session at the meeting.
“The question here really is whether an HER2-specific approach is superior to what we would offer to these patients in the standard of care setting,” McRee said.
She noted that the patients in DESTINY-CRC01 were “heavily pretreated…and if you think about what our options are in the refractory setting, we do have two approved treatments: regorafenib [Stivarga, Bayer] and TAS-102 [Lonsurf, Taiho Oncology].”
The current data suggest, however, that T-DXd is associated with a trend toward higher response rates and improved survival outcomes, as well as lower monthly costs.
“Without a doubt, this trial is clinically relevant,” she said, adding that it’s “important not to miss these patients.”
“They are rare…but I would argue that testing for HER2 amplification in colorectal cancer should be considered standard of care,” she said.
She added that, based on the current evidence, the trial “may be” practice changing, although it is “still to be determined how to sequence HER2 targeted therapies.”