T-DXd Tied to Encouraging Survival in HER2-Expressing Gyn Cancers

SEOUL, South Korea — Durable responses with trastuzumab deruxtecan (T-DXd; Enhertu) in heavily pretreated HER2-expressing gynecologic cancers appeared to translate into clinically meaningful survival outcomes, findings from a single-arm phase II trial suggested.

In DESTINY-PanTumor02, median progression-free survival (PFS) ranged from 5.9 months in women with ovarian cancer, to 7.0 months in those with cervical cancer, to 11.1 months in the endometrial cancer subgroup, Jung-Yun Lee, MD, of Yonsei University College of Medicine in Seoul, reported here.

Overall survival (OS), meanwhile, reached 13.2 months, 13.6 months, and 26 months, respectively, according to findings presented at the annual meeting of the International Gynecologic Cancer Society and recently published in the Journal of Clinical Oncology.

‘These data suggest that T-DXd is a potential treatment for patients with these gynecologic HER2-expressing tumors who have disease progression on prior therapy,” said Lee.

As has been previously reported, roughly half of the women with these gynecologic cancers responded to treatment — including 45% of the ovarian subgroup, 50% of the cervical subgroup, and 57.5% of the endometrial subgroup — with median durations of response (DORs) of 11.3 months, 14.2 months, and not reached, respectively.

Lee noted that overall response rates (ORRs) and overall survival (OS) were particularly encouraging among patients with the highest level of HER2 expression — immunohistochemistry (IHC) 3+.

The findings came from DESTINY-PanTumor02, an international open-label trial testing T-DXd in gynecologic, bladder, biliary tract, and pancreatic cancers, along with other tumor types. In the full study population of 267 patients, T-DXd yielded an ORR of 37%, a median DOR of 11.8 months, a median PFS of 6.9 months, and a median OS of 13.4 months.

And across the full study population, patients with the highest levels of HER2 tumor expression had the best outcomes: ORR of 61%, median DOR of 22 months, median PFS of 11.9 months, and a median OS of 21.1 months.

At the meeting here, Lee presented detailed data on the gynecologic cancer cohorts, which each included 40 patients.

Among the patients with ovarian cancer, the PFS rate at 1 year was 31.6% while the OS rate at 1 year was 57%. The 11-patient group with IHC 3+ expression had a median PFS of 7.4 months, a median OS of 20 months, and 64% responded to therapy. For the 19 patients with ICH 2+ expression, median survival values were 8.2 months and 13 months, respectively.

In the group with cervical cancer, the 1-year PFS and OS rates were 30% and 59%. Median PFS and OS were not reached for the eight patients with IHC3+ tumors, a group with an ORR of 75%. In the 20 patients with IHC 2+ expression, median PFS and OS were 4.4 months and 11.5 months.

Among the endometrial cancer patients, treatment yielded 1-year PFS and OS rates of 49% and 69%. Among the 13 patients with IHC 3+ tumors, median PFS was not reached, median OS increased to 26 months, and 85% responded to treatment. In the 17 patients with IHC 2+ expression, median PFS and OS were 11 months and 16.4 months, respectively.

Regarding safety, Lee noted that adverse events were “consistent with the established profile for T-DXd,” but also observed that pulmonary adverse events — particularly interstitial lung disease (ILD)/pneumonitis — “remain an important identified risk.”

While most cases in this trial were reportedly low grade and manageable (with an overall incidence consistent with prior studies), there were three adjudicated ILD-related deaths associated with treatment.

“Proactive monitoring, early detection, and active management are critical in preventing high-grade ILD/pneumonitis,” said Lee.