The Targeted Pulse: Endometrial Cancer Scores Multiple FDA Approvals, T-DXd Shows Promise in Breast Cancer, and More

Pembrolizumab/Chemotherapy Extends Approval Streak in Endometrial Cancer

The combination of pembrolizumab (Keytruda) plus chemotherapy is now FDA approved for patients with primary advanced or recurrent endometrial carcinoma, regardless of mismatch repair (MMR) status. In the phase 3 NRG-GY018/KEYNOTE-868 study (NCT03914612), the combination demonstrated survival benefits when compared with chemotherapy alone, which is the basis for the FDA’s approval. Pembrolizumab is now the first immunotherapy recommended for advanced endometrial carcinoma regardless of MMR status in the frontline setting.

“Endometrial cancer is the most common type of gynecological cancer, and frontline treatment options are limited for patients with advanced stage or recurrent disease,” said Ramez Eskander, MD, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center, in a press release. “The use of [pembrolizumab] in this setting has the potential to address a significant unmet need for these patients.”

Another Victory for Endometrial Cancer With Durvalumab Plus Chemotherapy

The FDA has approved durvalumab (Imfinzi) with carboplatin plus paclitaxel, followed by single-agent durvalumab for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). The phase 3 DUO-E trial (NCT04269200) showed that the combination significantly improved progression-free survival (PFS) when compared with placebo. The improvement was specifically elicited in patients with dMMR tumors, based on an exploratory analysis of MMR status.

“The bottom line is our primary analysis was positive, and that combination does work more than the control arm of chemotherapy,” Shannon Westin, MD, MPH, FACOG, director, Early Drug Development, and professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, previously told Targeted Oncology^TM in an interview.

Amivantamab/Chemotherapy Leads to Significant PFS Benefit in NSCLC

When combined with chemotherapy, amivantamab-vmjw (Rybrevant) significantly prolonged PFS for patients with EGFR-mutant advanced non–small cell lung cancer (NSCLC) who had progressed on osimertinib (Tagrisso). In the phase 3 MARIPOSA-2 study (NCT04988295) the combination was compared with chemotherapy alone, and in addition to significantly improving PFS, the combination also prolonged time to treatment discontinuation, time to start of subsequent treatment, and second PFS compared with chemotherapy alone.

“At a median follow-up of 8.7 months, amivantamab with chemotherapy reduced the risk of progression or death by 52%,” Ryan D. Gentzler, MD, said in a presentation of the data at the European Lung Cancer Congress 2024. Gentzler is a thoracic medical oncologist and associate professor of medicine in the Division of Hematology/Oncology at the University of Virginia Cancer Center in Charlottesville.

T-DXd Success Leaves Treatment Gaps in Breast Cancer With Brain Metastasis

Trastuzumab deruxtecan (Enhertu; T-DXd), a newer antibody drug conjugate (ADC), significantly surpasses older ADCs such as T-DM1 (trastuzumab emtansine; Kadcyla) in the treatment of HER2-positive breast cancer with baseline brain metastases. However, the verdict is still out on whether T-DXd meets an unmet need for those with HER2-low breast cancer, active HER2-positive breast cancer, and other solid tumors who have brain metastases. In an interview with Targeted Oncology^TM, Sarah Sammons, MD, reviews the T-DXd data from an exploratory analysis of the DESTINY-Breast03 trial (NCT03529110) and a retrospective analysis from the DESTINY-Breast04 clinical trial (NCT03734029).

“T-DXd is FDA-approved in patients with metastatic breast cancer that have low expression, so now we are investigating whether T-DXd works for patients with low levels of HER2 and brain metastasis. We have a small amount of data in HER2-low brain metastasis so far. The patients with brain metastasis were analyzed retrospectively from the DESTINY-Breast04 clinical trial, and it’s looking like there is an intracranial response rate around 25% in those patients, which for HER2-low or historically, HER2-negative brain metastasis is respectable,” Sammons said in the interview. Sammons is a medical oncologist, clinical investigator in the Breast Oncology Center, associate director of the Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, Boston, MA.

Repotrectinib Receives Accelerated Approval for NTRK-Positive Solid Tumors

An accelerated FDA approval was granted to repotrectinib (Augtyro) for both adult and pediatric patients (aged 12 or older) who have locally advanced or metastatic solid tumors that harbor an NTRK gene fusion and where surgical resection is likely to result in severe morbidity. The approval is based on data from the phase 1/2 TRIDENT-1 study (NCT03093116) where investigators evaluated patients with advanced solid tumors, including ROS1 fusion-positive NSCLC.

“What’s different about repotrectinib, what makes it more appealing or possibly a best in class, is actually the way the drug has been restructured or designed to overcome some of the acquired resistance mutations, which translates into a better durability of response. Also, it had excellent central nervous system penetration, as we’ve seen now with the TRIDENT-1 study,” Firas B. Badin, MD, the medical director of oncology research at the Baptist Health Medical Group in Lexington, Kentucky, told Targeted Oncology^TM in an interview.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.