Kohei Shitara, MD

At the ASCO session on the phase II DESTINY-PanTumor02 trial on T-DXd, the invited discussant, Kohei Shitara, MD, commented: “As expected, this trial demonstrated a very impressive response rate and duration of response” and “showed T-DXd [fam-trastuzumab deruxtecan-nxki] to be a potential new treatment option for patients with HER2-expressing solid tumors.” Dr. Shitara is Director of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan.

The response rates of 37.1% overall and 61.3% in immunohistochemistry (IHC) 3+ patients support tumor-agnostic development for T-DXd, he said. This overall response rate is in the range of that shown in studies leading to the approval of other agents in tumor-agnostic indications: 29.0% to 39.6% with pembrolizumab, 41.6% with dostarlimab-gxly, 41% with dabrafenib plus trametinib, 44% with selpercatinib, 57% with entrectinib, and 75% with larotrectinib. The similarity of the response rate to those achieved in breast, gastric, and lung cancers—where the drug is approved—qualify T-DXd for exploration in new indications, according to Dr. Shitara. “I believe the results from the current study warrant further discussion with the regulatory authorities,” he added.

Testing for HER2 expression, however, remains challenging, Dr. Shitara acknowledged. Tissue IHC is widely used but suffers from interobserver variability; discordance between local and central testing was around 20% in this study. As of now, there are no guidelines in the tumor-agnostic setting, he said. “Quality assurance is needed for HER2 IHC testing,” he noted.

Additional Thoughts on IHC Testing

Despite concerns about IHC testing, ASCO expert Bradley Alexander McGregor, MD, of Dana-Farber Cancer Institute and Harvard Medical School, pointed out in a press briefing that IHC testing is “easily done in local pathology labs,” giving physicians quick information about the HER2 biomarker, so targeted treatment can be facilitated. “That’s one of the good things…. And as we start having treatments that can make a difference, I think we will have to start thinking about [broader] testing,” he said.

Bradley Alexander McGregor, MD

“This study provides data for an unmet need for patients who have exhausted standard therapeutic options with tumors that overexpress HER2 for which no drug is yet approved,” Dr. McGregor added. “Although additional follow-up is needed, there is robust activity across multiple HER2-expressing tumors…coupled with an encouraging safety profile. T-DXd could provide a new treatment option for these patients.” 

DISCLOSURE: Dr. Shitara reported financial relationships with AbbVie, Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Guardant Health, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, and Janssen. Dr. McGregor has served as a consultant or advisor to Seattle Genetics/Astellas, Exelixis, Astellas Pharma, Genentech/Roche, Pfizer, EMD Serono, Eisai, Bristol Myers Squibb, Calithera Biosciences, and Merck CgA.