Akihiro Ohba, MD, discussed the potential benefits of T-DXd in HER2-expressing biliary tract cancer.
Results from the single-arm phase 2 HERB trial (NCCH1805; JMA-IIA00423) of trastuzumab deruxtecan (Enhertu; T-DXd) in patients with HER2-expressing unresectable or recurrent biliary tract cancer (BTC) were recently presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and indicated promising efficacy across 22 patients.
Akihiro Ohba, MD, an investigator at the National Cancer Center Hospital in Japan and lead investigator of this study, spoke with CancerNetwork® about the efficacy of T-DXd in patients with HER2-expressing BTC.
Results indicated a confirmed objective response rate (ORR) by blinded independent central review of 36.4% (90% CI, 19.6%-56.1%), comprised of 2 complete responses (9.1%) and 6 partial responses (27.3%), in patients with HER2-expressing BTC treated with T-DXd, indicating a statistically significant improvement (P = .01). Additionally, the median progression-free survival (PFS) among these patients was 4.4 months (95% CI, 19.6-56.1) and the median overall survival (OS) was 7.1 months (95% CI, 4.7-14.6). The treatment showed efficacy even in patients with HER2-low BTCs, with an ORR of 12.5% (1/8; 1 PR; 95% CI, 0.3-52.7) and PFS of 4.2 months (95% CI, 1.3-6.2). Adverse events of grade 3 or higher occurred in 81.3% (26/32) of patients, most commonly anemia (53.1%), neutropenia (31.3%), and leukopenia (31.3%). Investigators concluded that these results warranted further development of T-DXd as a possible approved treatment for HER2-positive cancers.
Ohba: We started to design this trial in 2016. At that time, there were no effective secondary treatments for BTC. The activity of T-DXd in breast cancer [had already showed] early signs of efficacy. We also knew that HER2 positivity in BTC is estimated to affect about 20% to 30% of patients, similar to rates in gastric and breast cancer. Therefore, we thought this drug might also be active for BTC and started to conduct this trial.
The primary end point was the confirmed ORR in HER2-positive BTCs, which was met with a rate of 36.4%. This was what we expected.
The most common adverse events were hematologic toxicities, such as anemia or decreased neutrophil count, which is similar to what is seen in other T-DXd trials. We also saw interstitial lung disease [ILD] which is a known risk with this drug. We had 25% of patients develop ILD, including 2 fatal [grade 5] cases.
We now need to examine the biopsy analysis, including circulating tumor DNA [ctDNA], which will tell us some information. We also need to conduct comparisons with registry data because HER2-positive BTC is in a very limited population, [which may result in] difficulties conducting large-scale phase 3 trials. We need to confirm survival benefit [in this population as compared with] HER2 wild-type populations.
The key takeaway of this trial is the efficacy of T-DXd in patients with BTC. BTC has many treatments, some of which are supported by clinical trials, such as pemigatinib [Pemazyre] and infigratinib [Truseltiq] for FGFR2 fusions. However, for HER2-positive cancers, no drugs have been approved by either the FDA or the Japanese PMDA [Pharmeceuticals and Medical Devices Agency], and so we need to proceed to the next step for drug approval.
Ohba A, Morizane C, Kawamoto Y, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): An investigator-initiated multicenter phase 2 study (HERB trial). J Clin Oncol. 2022;40(16) 4006. doi:10.1200/JCO.2022.40.16_suppl.4006