Questions Remain Around Neoadjuvant Chemoimmunotherapy in TNBC

Roshni Rao, MD, FACS

NewYork-Presbyterian/Columbia University Irving Medical Center

Treatment with neoadjuvant chemoimmunotherapy led to higher perioperative events compared with chemotherapy in patients with triple-negative breast cancer (TNBC); however, differences in complications were not significant, according to an institution review following the KEYNOTE-522 trial (NCT03036488) presented at the 25th American Society of Breast Surgeons Annual Meeting.

Investigators evaluated 26 patients with TNBC who received preoperative pembrolizumab (Keytruda), with or without chemotherapy, compared with 26 patients with TNBC who received preoperative chemotherapy alone. Results showed that, when comparing overall risks of the complications evaluated, the chemoimmunotherapy group experienced a higher overall risk compared with the chemotherapy group (relative risk, 2.5; 95% CI, 1.05- 6.56; P = .0357).

In an interview with CancerNetwork, Roshni Rao, MD, FACS, chief of the Breast Surgery Program at NewYork-Presbyterian/Columbia University Irving Medical Center, discussed the use of neoadjuvant chemoimmunotherapy in patients with TNBC, as well as next steps in the breast cancer surgery landscape.

CancerNetwork: Is there anything in particular about the safety findings from this institution review that oncologists should know about from the trial?

Rao: Immunotherapy is fantastic. There’s no doubt that it’s the wave of the future in all sorts of cancers, and it seems to work very well for specific [patients with] triple-negative cancer. But there are repercussions and I, myself, have had patients who have gone into significant adrenal failure after receiving immunotherapy. It can be a lifelong problem. We have to weigh the risks and benefits of it. The other thing that remains to be seen that we just don’t know yet is: should we be waiting longer after immunotherapy to do surgery?

It’s always the balance, right? Normally we say 3 to 6 weeks [after treating with immunotherapy], and that just seems to be the right time. There are some data to say that 3 to 4 weeks is better. But we don’t have great data on that specific issue. Should we be doing things differently? Should we be managing the patient’s glucose differently, or should we be intraoperatively closing the incisions in a different way? Those are the things that we just don’t know.

Are there other factors we should be looking at to determine procedure time?

If you do a lumpectomy in a sentinel node, that’s just going to overall be less risky than when you’re doing a mastectomy, or expander, which is a foreign body, or if you’re doing abdominal flap reconstruction at the same time. Maybe in those patients, we should be waiting longer. Then in the patients who are having smaller procedures, it’s okay to do it right away.

Looking ahead, how do you think the design of future studies can be improved to better understand the impact of neoadjuvant chemoimmunotherapy on perioperative outcomes in these patients?

We should be following these complications, which we do as part of the initial trials, but we should be doing that carefully as a group and looking at the timeframe. I-SPY has an immunotherapy arm as well. Some of the data will come out that the complication rates overall in breast surgery are still low. Being able to parse out, even if you double the complication rate, you go from a 1% [occurrence of] hematomas to 2%, so you’re going to need large data sets to clarify what the risk is, and then you’re going to need even larger data sets to sort out what interventions make the difference.

It’s key for patients to also be a part of their treatment decisions. Do you have any advice for your colleagues on how to present complications to the patient and make sure that they’re getting involved in their treatment decisions?

There’s a lot of excitement around immunotherapy. But like everything else, there are risks to it. If you do have some of the more aggressive cancers, it’s worth it to take on those risks. I don’t think we should shy away from that, and someone may really benefit [from immunotherapy before surgery].

What are you hopeful for as the next big thing in breast cancer surgery?

I really like the idea that we continue to de-escalate [therapy]. I remember, even in my own practice, when I started, I used to tell patients that if your tumor ends up being more than 1 cm, or you have 1 lymph node positive, you’re going to need chemotherapy. I just used to say that because that was what happened, right? But now, if you have a low [Oncotype DX score], even if you have 3 positive nodes, you don’t need chemotherapy; you can just take this medication instead. Now we have much more targeted treatments that minimize what used to be a scary diagnosis.

Reference

Switalla K, Boughey J, Dimitroff K, et al. The role of clipping the lymph node in clinically node-positive patients treated with neoadjuvant chemotherapy for breast cancer: impact on axillary surgery in the ISPY-2 clinical trial. Presented at: The American Society of Breast Surgeons 25th Annual Meeting; April 10-14, 2024; Orlando, FL. Abstract 1678051.