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MBC Applying New Developments

CE / CME

Applying the Latest Developments in Metastatic Breast Cancer Through Education of Healthcare Professionals, Patients, and Caregivers

Nurses: 1.50 Nursing contact hours

Physicians: maximum of 1.50 AMA PRA Category 1 Credits™

Pharmacists: 1.50 contact hours (0.15 CEUs)

Released: October 19, 2023

Expiration: October 18, 2024

Joyce O'Shaughnessy
Joyce O'Shaughnessy, MD
CME/CE Information

Activity

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Takeaways for Learners

In terms of take-home messages, we want to be aware of documented survival advantages in metastatic trials—particularly the phase III trials, but also very promising phase II randomized trials. We always want to offer to all our patients the best therapy that can prolong their survival.

In the HR-positive/HER2-negative space, we are individualizing treatment for patients. We start with a CDK4/6 inhibitor plus ET for all patients, or with an AI, unless they are recurring on an AI, in which case they receive fulvestrant. Upon progression, they can be considered for elacestrant if they have an ESR1 mutation. I must stress that we want to be analyzing ctDNA in these patients to look for an ESR1 mutation after progression on the first-line CDK4/6 inhibitor. If you do not find a mutation, you want to check ctDNA again after progression on the second-line regimen and again after progression on the third-line regimen, because the chances of finding it go up the more heavily pretreated patients are with ET, and we do not want to miss the opportunity to give patients an oral SERD if applicable.

In patients with PI3KCA mutation in the metastatic/recurrent setting, I offer alpelisib. With alpelisib, some physicians give the full starting dose of 300 mg of treatment to robust patients. I do tend to reduce the dose to 250 mg to ensure that I can get patients to tolerate therapy. If they do well, I may go up to 300 mg, but sometimes I have to go down to 200 mg because I am determined to get patients to tolerate alpelisib. I manage the blood sugar very proactively by having patients eat a low-carbohydrate diet, ensuring that their hemoglobin A1C is <6.5%, checking their blood sugar at home with a fingerstick, and starting metformin prophylactically. This approach is supported by preliminary results from the METALLICA trial, where metformin was started prophylactically.63 Based on that, I start metformin 500 mg for the first few days of alpelisib, go up to 500 mg twice daily, and then escalate from there if the blood sugar gets above 160 mg/dL. I hope that in the not-too-distant future, we may be able to offer capivasertib plus fulvestrant if they have an AKT-pathway alteration. No doubt I will be looking for AKT mutations and PTEN loss, as well.

We may want to consider a PARP inhibitor (olaparib or talazoparib) in those with germline BRCA or PALB2 mutations based on available data.5,31 I look for somatic BRCA mutations to remind me to make sure I get that germline testing. Then, when they need cytotoxic therapy, they can go on to receive capecitabine and then either T-DXd if they have disease that is HER2 low or sacituzumab govitecan if their disease is HER2 zero.

I also watch for new HER2 mutations in patients with HR-positive/HER2-negative disease to be able to recommend neratinib plus trastuzumab and fulvestrant to appropriate patients.

In the first-line HER2-positive setting, the CLEOPATRA regimen is the standard of care, although I dare say that T-DXd will replace the CLEOPATRA regimen. The median PFS with T-DXd in the DESTINY-Breast-03 trial was 28 months compared with 18.5 months with pertuzumab/trastuzumab/docetaxel in the first-line CLEOPATRA trial.51,64 So, it is likely that T-DXd will become the first‑line standard, perhaps with or without pertuzumab. We will watch that space carefully. But right now, T-DXd is our second‑line standard of care, unless the patient has only brain metastasis or very little disease outside the brain. The brain is clearly the most important site of metastasis in a small minority of patients who, I believe, should receive tucatinib plus capecitabine and trastuzumab based on the evidence from the HER2CLIMB trial.55,65 If patients receive T-DXd as second-line treatment, they should receive the regimen of tucatinib with capecitabine and trastuzumab in the third-line setting and then T-DM1 as fourth-line therapy. We also can use T-DM1 with niraparib for patients with brain metastasis.  

In TNBC, we have to know the PD-L1 status of the disease. In the first-line setting, if the disease is PD-L1 CPS ≥10, standard first-line treatment is chemotherapy plus pembrolizumab. Otherwise, it is chemotherapy or a PARP inhibitor if they have a germline BRCA mutation. In the second-line or later setting, sacituzumab govitecan is my agent of choice. I generally reserve T-DXd after sacituzumab govitecan, because sacituzumab has level 1 evidence from the phase III ASCENT trial showing improvement in OS. I may reserve T-DXd for those with HER2-low disease. In general, we should start with full-dose treatment of sacituzumab govitecan, unless we have a frail patient where we are concerned, as previously discussed. Then it is prudent to start with a reduced dose of treatment and dose escalate if they are tolerating treatment well. We also want to be proactive at keeping our eye on toxicities such as ILD/pneumonitis with T-DXd and severe neutropenia and diarrhea with sacituzumab govitecan, managing those appropriately so we can maintain patient adherence with an active therapy without affecting quality of life.

 Salvage regimens might include eribulin and gemcitabine/carboplatin. Of course, clinical trials are absolutely key for these patients. We also look forward to having dato-DXd approved in the metastatic setting.

Go Online for More CCO Coverage of Breast Cancer!

I invite you to visit the program page to access downloadable slides, clinical commentaries, and interactive decision support tools that will inform selection of appropriate therapy for your patients with advanced/metastatic breast cancer.

In addition, I encourage you to download the helpful point-of-care resources that are part of a patient communication checklist to share with your patients.

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