T-DXd Proves Mettle in Multiple Solid Tumors

CHICAGO — Trastuzumab deruxtecan (T-DXd, Enhertu) turned in promising results in a range of HER2-expressing solid tumors, according to interim findings from the DESTINY-PanTumor 02 (DPT02) trial.

In patients with cervical cancer, endometrial cancer, ovarian cancer, biliary tract cancer, and bladder cancer, T-DXd yielded an overall objective response rate (ORR) of 37% and a median duration of response (DOR) of 11.8 months. Those numbers were even better — an ORR of 61% and DOR of 22 months — among patients with HER2 expression with an immunohistochemistry (IHC) score 3+, reported Funda Meric-Bernstam, MD, of the University of Texas MD Anderson Cancer Center in Houston.

However, T-DXd did not fare as well in pancreatic cancer, she said at a press briefing at the American Society of Oncology (ASCO) annual meeting.

Still, “DPT02 indicates broad activity with trastuzumab deruxtecan across HER2-expressing advanced solid tumors where there are currently no approved HER2-targeted therapies,” Meric-Bernstam said. “These results could help provide an important new therapy for patients who face poor prognosis.”

The trial is ongoing and other survival outcomes will be reported in the future, according to the researchers.

T-DXd has become standard of care in breast cancer, advanced metastatic gastric cancer, and HER2/ERBB2-mutant non-small cell lung cancer, they stated.

ASCO discussant Bradley McGregor, MD, of the Dana-Farber Cancer Institute in Boston, said he was impressed with the activity of T-DXd seen in the overall DPT02 population.

“HER2 expression has been around a long time, and we think about this all the time in breast cancer,” he said. “But HER2 is expressed in all the tumors as well. And that really represents an unmet need. This is really compelling data, that by using antibody-drug conjugate, we can deliver the chemotherapy by taking that target right to the source.”

“Aside from pancreatic cancer, we actually are seeing really encouraging results with no new safety signal. So while this is still early data, I think this is really exciting news and represents a shift in how we think about cancer care,” McGregor said.

DPT02 is an open-label, multicenter study for patients with advanced solid tumors positive for HER2 expression (IHC 2+ or 3+) who are ineligible for curative therapy. Patients were a second-line treatment population, the researchers explained, and were allowed to have gotten prior HER2-targeted therapy. T-DXd was administered at 5.4 mg/kg every 3 weeks.

The plan was for 40 patients in each of seven cohorts — cervical, endometrial, ovarian, biliary tract, bladder cancer, and one for rare cancers. Only 25 pancreatic cancer patients were enrolled, and an extra was enrolled in a couple of the other groups, so the total number of participants added up to 267. Breast cancer, non-small cell lung cancer, gastric cancer, and colorectal cancer were excluded. The data cutoff for the current analysis was November 2022.

The pancreatic cancer patients were outliers compared with the other groups. They had no complete responses, one partial response, and 17 patients with stable disease, which translated to a disease control rate of 36% and an overall response rate of just 4.0%. The median duration of response has not been reached in this group.

Independent central review pointed to a 36.7% ORR overall and disease control rate at 12 weeks of 68.2%. For the individual groups, those rates were:

• In cervical cancer, 50.0% and 67.5%, with a median DOR of 9.8 months
• In endometrial cancer, 57.5% and 80%, with the median DOR not having been reached
• In ovarian cancer, 45.0% and 70%, with a median DOR of 11.3 months.
• In biliary tract cancer, 22.0% and 65.9%, with a 8.6-month DOR.
• In bladder cancer, 39.0% and 70.7%, with a median DOR of 8.7 months
• With other solid tumors, 30.0% and 75%, with the median DOR not having been reached

The complete response rate for the entire population was 5.6%. The highest complete response rate was seen in endometrial cancers, at 17.5%. The overall rate of partial response was 31.5%, including a 45% rate in the cervical cancer group, 40% in the endometrial cancer group, and 36.6% in bladder cancers.

Meric-Bernstam’s group also reported that patients with higher IHC scores generally had better responses. For example, in cervical cancer, 75% of women with IHC 3+ achieved an ORR versus 40% among those with an IHC 2+ score, while in endometrial cancer, ORRs were 84.6% and 47.1%, respectively. However, in pancreatic cancer, the ORR was 0.0% for IHC 3+ and 5.3% for IHC 2+.

The most common treatment-emergent adverse events were nausea (54.3%), followed by fatigue (37.8%), and neutropenia (32.6%). There was one death in the study population. Overall, T-DXd adverse events in the trial were in line with the agent’s known safety profile, according to the researchers.