Novel Triplet Therapy in Patients With Metastatic Uterine Serous Carcinoma


Collaborative discussion on the advent of triplet therapy in patients with metastatic uterine serous carcinoma and clinical data behind this strategy.


Robert L. Coleman, MD, FACOG, FACS:This patient is untreated. You took her to surgery, and she’s recovering. [She has] a HER2 [human epidermal growth factor receptor 2]–amplified tumor. Amanda Nickles Fader did this randomized phase 2 [trial] looking at paclitaxel [Abraxane]–carboplatin [Paraplatin] plus or minus trastuzumab [Herceptin]. She was able to demonstrate in this relatively small study that there seemed to be a benefit with the addition of trastuzumab in this patient population. Kimberly, have you had much experience with using trastuzumab in the gynecologic space?

Kimberly Halla, MSN, FNP-C: We’ve just started using it religiously with patients who have cancer. But it’s hard to get that pathology, to add to that HER2 amplification. It takes us a little while to get those results. We want to start the trastuzumab right away. Unfortunately, we might find we’re delayed at some point.

Robert L. Coleman, MD, FACOG, FACS: Good point. In the trial, for the patients who advanced or recurrent [disease], the hazard ratios were all pointing in the same direction, regardless of whether they presented that way or had recurrent uterine serous. What was really interesting though is if they’d had prior chemotherapy, they didn’t see a big benefit to this additional line of therapy with trastuzumab. There’s more nuance to this, and we need to confirm this in a larger trial because this is a relatively small sample size. But the triplet [therapy] produced an improvement in progression-free survival across the entire population, with a 50%-plus reduction in the hazard [ratio] from regression or death. There’s a stronger effect in patients who presented in the first line with advanced disease, with a hazard ratio of 0.44. These are very impressive data.

When we looked at overall survival, we saw in the all-comers population that there was a reduction in the probability for death of about 42%. A lot of that was driven by patients like this, who presented in the first-line setting with a hazard ratio of 0.49. This particular drug isn’t something we use all the time, but it’s something we see. Obviously, there’s a lot of experience with it in the medical oncology community when it’s approved for breast cancer. But it’s also being used in other diseases, like gastric [cancer] and other tumors. Michael, is this a tolerable regimen?

Michael J. Birrer, MD, PhD: It is, and it’s interesting that we have these data, but I’ve probably treated more breast cancer with this agent than gynecologic cancers, and there’s a real difference in the sense that we worry about cardiac toxicity because these patients [with breast cancer] are on it much longer than these patients, for good or bad. To me, you’re seeing a very tolerable regimen. It bumps up a little in the experimental arm, but it’s all manageable. I don’t see anything that’s a problem.

Krishnansu S. Tewari, MD:There are other HER2-targeting agents. Why can’t we use 1 of those?

Robert L. Coleman, MD, FACOG, FACS:That’s the next step. There are many nice compounds that we could use in this case. Kimberly, what’s been your office experience with tolerability of this triplet?

Kimberly Halla, MSN, FNP-C: It’s been very tolerable in all settings, and we take the lead from the breast oncologist as well. We’re making sure their echocardiograms are done and that they’re safe to remain on this medication, but it’s very well tolerated.

Robert L. Coleman, MD, FACOG, FACS:I love it. This patient ended up getting that triplet [therapy] because they listened to you. They ended up going on for quite a bit and tolerating it well, and it looks like it was very consistent with the data that we saw in the study.

Transcript edited for clarity.

Related Videos
Video 11 - "Treating Patients With RCC Who Progress Following Adjuvant Therapy"
Video 10 - "RCC: Informing Treatment Decisions with Clinical Trial Data"
Video 9 - "KEYNOTE-564: Adjuvant Pembrolizumab in Renal Cell Carcinoma"
Video 8 - "Adjuvant Immunotherapy in Renal Cell Carcinoma"
Video 7 - "Case 2: A 48-Year-Old Man with Renal Cell Carcinoma"
Video 7 - "Emerging Therapies for Refractory cGvHD: Potential Advantages of Axatilimab"
A panel of 3 experts on GVHD
Related Content