Trastuzumab deruxtecan shows ‘broad activity’ in HER2-expressing solid tumors
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Key takeaways:
- Trastuzumab deruxtecan induced responses in multiple tumor types.
- The agent conferred the highest ORRs and most durable responses among patients with the highest level of HER2 expression.
CHICAGO — Trastuzumab deruxtecan showed clinically meaningful activity against several types of HER2-expressing solid tumors, according to interim results of the DESTINY-PanTumor02 study presented at ASCO Annual Meeting.
The HER2-directed antibody-drug conjugate, also known as T-DXd (Enhertu; AstraZeneca, Daiichi Sankyo), demonstrated the highest objective response rates and most durable responses among patients with the highest level of HER2 expression.
“T-DXd has broad activity and could present a new therapy option in patients [with HER2-expressing tumors],” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, said during a press conference.
Background, methodology
Trastuzumab deruxtecan has emerged as a standard of care for multiple advanced cancers, including HER-expressing breast cancer, HER2-positive gastric/gastroesophageal junction cancer and HER2-mutant non-small cell lung cancer. HER2 expression occurs in several other types of solid tumors, although testing is not routine.
“For these patients, there are no approved HER2-targeted treatments, and often the disease is refractory to standard-of-care therapies,” Meric-Bernstam said.
Early-phase studies of trastuzumab deruxtecan have shown antitumor activity in other cancers that express HER2, including colorectal, salivary gland, biliary tract and endometrial cancers, she added.
The open-label, multicenter DESTINY-PanTumor02 trial assessed the antibody-drug conjugate at a dose of 5.4 mg/kg every 3 weeks among 267 patients (average age, 62 years; 61% white, 32.6% Asian) with HER2-expressing locally advanced or metastatic solid tumors not eligible for curative therapy. Tumor cohorts included biliary tract, bladder, cervical, endometrial, ovarian, pancreatic and other tumors excluding breast, gastric, colorectal and NSCLC.
Investigator-assessed confirmed objective response rate served as the primary endpoint, with duration of response, disease control rate, PFS, OS and safety as secondary endpoints.
Median follow-up was 9.7 months at data cutoff on Nov. 16, 2022.
Results, next steps
Researchers observed an ORR of 37.1% among all patients and median duration of response of 11.8 months (95% CI, 9.8 to not estimable). Almost half of patients (46.1%) had stable disease.
Patients with HER2 expression by immunohistochemistry [IHC] of +3 (n = 75) had a higher ORR (61.3%) and longer median duration of response (22.1 months; 95% CI, 9.3 to not estimable). Patients with IHC +2 had an ORR of 27.2% and median duration of response of 9.8 months (95% CI, 4.2-12.6).
The endometrial cancer cohort had the highest ORRs (all, 57.5%; IHC 3+, 84.6%; IHC +2, 47.1%), followed by the cervical cancer (all, 50%; IHC 3+, 75%; IHC +2, 40%), ovarian cancer (all, 45%; IHC 3+, 63.6%; IHC +2, 36.8%), bladder cancer (all, 39%; IHC 3+, 56.3%; IHC +2, 35%), other (all, 30%; IHC 3+, 44.4%; IHC +2, 18.8%) and biliary tract cancer (all, 22%; IHC 3+, 56.3%; IHC +2, 0%) cohorts. The pancreatic cancer cohort had only one response by investigator assessment and three responses by central review.
The toxicity profile of trastuzumab deruxtecan appeared consistent with that observed in other clinical trials of the agent, with 58.4% of patients experiencing grade 3 or higher adverse events. The most common adverse events included nausea (54.3% overall, 3.4% grade 3), fatigue (37.8% overall, 6% grade 3), neutropenia (32.6% overall, 19.1% grade 3) and anemia (25.8% overall, 8.6% grade 3).
A total of 8.2% of patients stopped treatment due to drug-related adverse events.
Twenty patients (7.5%) experienced adjudicated drug-related interstitial lung disease/pneumonitis, including one grade 3 or higher and one grade 5 or higher case.
Researchers will analyze OS and PFS with additional follow-up as the trial continues, Meric-Bernstam said.
References:
- ASCO: HER2-targeted antibody drug conjugate shows strong antitumor activity and durable responses across multiple tumor types (MD Anderson press release). Available at: https://www.mdanderson.org/newsroom/asco-her2-targeted-antibody-drug-conjugate-shows-strong-anti-tumor-activity-and-durable-responses-across-multiple-tumor-types.h00-159619434.html. Published June 5, 2023. Accessed June 5, 2023.
- Meric-Bernstam F, et al. Abstract LBA3000. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
Perspective
Back to TopBradley Alexander McGregor, MD
HER2 expression has been around for a long time. We think about it all the time in breast cancer and drugs that are approved there, but HER2 is expressed in other tumors, as well, and that really represents unmet need because we have limited options in this situation.
I think this is really, really compelling data using T-DXd, delivering the chemotherapy by taking that target right to the source. Aside from pancreatic cancer, we saw encouraging results with no new safety signals.
While early, I think this is really exciting and represents a shift in how we think about cancer care.
Dana-Farber Cancer Institute
Harvard Medical School
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Meric-Bernstam F, et al. Abstract LBA3000. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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