Breast Cancer Clinical Case Review

Mridula George, MD, assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, and associate program director for breast medical oncology program in the division of medical oncology at Rutgers Cancer Institute of New Jersey, presents the results and discusses toxicities, progression and other considerations when approaching treatment for patients with HER-2 positive metastatic breast cancer.

Editor’s note: The following is an automatically generated transcript of the above video.

"Coming back to this patient, so she was treated with docetaxel, trastuzumab, and pertuzumab and she had a response to therapy.

The breast mass was not palpable after two cycles of treatment. And re-staging scans were done at about eight weeks to assess the treatment response. On the CAT scan, the breast mass and the axillary lymph nodes were no longer visualized. And in terms of the liver lesion, there was a significant response. There were some residual hypodense lesion in the dome of the liver that measured 14 millimeters and it previously measured 5 centimeters. And the remainder of the liver lesions were no longer visualized. And the bone scan again was repeated and there was no evidence of osseous metastasis.

So based on these results, patient continued trastuzumab, pertuzumab, and completed six cycles of chemotherapy. And then she was maintained on maintenance trastuzumab and pertuzumab. Given that she was post-menopausal, letrozole was added as part of a treatment regimen.

Important things to consider when treating patients with this regimen. Alopecia is a common side effect with taxane based chemotherapy. Scalp cooling is something that can be considered to reduce the risk of chemotherapy induced alopecia, especially since patients are only getting six cycles of chemotherapy. There's no risk of alopecia with trastuzumab and pertuzumab when they're in the maintenance phase.

Taxanes also notorious for neuropathy, so monitor closely for chemotherapy induced neuropathy. Dose reduction should be considered, or the addition of gabapentin and Lyrica for neuropathy. As mentioned earlier, cardiotoxicity is a common problem with trastuzumab. The risk of LV dysfunction. And in the CLEOPATRA study, the risk of LV dysfunction was about 6.6% in the pertuzumab group and 8.6% in the control group. Dysfunction was reversible upon discontinuation of trastuzumab and pertuzumab. So it's important to monitor the ejection fraction while they're on treatment. Can be done every three month initially and then spaced out if the LVEF is stable. If there is any early evidence of left-ventricular ejection function dysfunction, then patients should be referred to cardio-oncology, and ACE inhibitors and beta blockers can be considered for the management of the LVEF dysfunction. And if patients have bone metastases, also consider the addition of bone modifying agents to reduce the incidence of skeletal related events.

Another important thing is biosimilars. So trastuzumab was first approved in 1998. And recently, in over the last five years, biosimilars have been approved. And they're all FDA approved. And these are the list of trastuzumab based biosimilars. There are five of them. And there's also a subq version of a combination of trastuzumab and pertuzumab, which is manufactured by Genentech. It's called PHESGO. And that can also be considered if patients are on maintenance trastuzumab and pertuzumab. The dosing guidelines should be fully assessed before patients are given these medications. They should not be substituted for any of the other HER2 based targeted therapies.

So, beyond progression, what are some of the recommendations? So, fam-trastuzumab deruxtecan-nxki is a Category 1 recommendation in the second line setting. Especially if patients have brain metastases, the combination of trastuzumab capecitabine with tucatinib can also be considered in the second line setting if the patients have brain metastases, but usually is used in the third line setting. Ado-trastuzumab, which was a prior preferred second line agent has now moved to the third line based on the DESTINY-Breast03 data."