Breast Cancer Clinical Case Review

In this video, Coral Omene, MD, PhD, assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, and program director of Breast Cancer Disparities Research in the division of medical oncology at Rutgers Cancer Institute of New Jersey, presents the results, and discusses residual disease options and other considerations when approaching treatment for patients with triple-negative breast cancer.

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

“This is what was offered to our patient. She was treated with the keynote 522 regimen and after treatment, the post-treatment bilateral breast MRI, showed that there was minimal background parenchymal enhancement observed, it was symmetrical.

The previously seen mass, which is a known malignancy in the upper inner quadrant of the right breast, was not demonstrated on this current study. And there was no MRI evidence for malignancy in the left breast. She subsequently underwent a right breast lumpectomy and sentinel lymph node biopsy. And the pathology results showed that there was no residual invasive ductal carcinoma observed, either in the mass, in the breast tissue, or in the lymph nodes. There was 0/2 lymph nodes that were involved. So she had achieved a pathologic stage ypT0ypN0, which is considered a pathologic complete response or a PCR.

Now, this patient had the best outcome that one could expect for a triple-negative breast cancer patient treated with new adjuvant therapy given a PCR.

However, there are patients that would not achieve a PCR and they would have residual disease. There are options for this patients. One, you could continue on adjuvant pembrolizumab as per the keynote 522 clinical trial. For the remaining cycles, this is standard of care, or if another new adjuvant regimen was used, one will consider adjuvant capecitabine as per the Create-X clinical trial.

If you look to the right of the slide, you would see published in 2017, New England Journal of Medicine. This was actually the first trial that offered more options for early stage triple-negative breast cancer patients in the setting of having a residual disease after, at the time of surgery, after pre-op systemic therapy. In this trial, patients that had residual disease were randomized to a control arm versus capecitabine arm, and you can clearly see that absolute disease-free survival was improved for those patients who went on to receive capecitabine either a 1,000 to 1,250 milligrams per squared, given twice daily on days 1-14, cycled every 21 days for 6-8 cycles. This patient achieved an absolute disease-free survival that was superior to control, and this translated to overall survival after three and a half year follow up. This negative breast cancer subset of patients had an absolute overall survival benefit of 8.5% higher dose in the control arm. So this is a standard of care regimen that can be given to patients who may have been treated with other regimens that are also efficacious, but do not involve the keynote 522 regimen.

Now, there are also other considerations for those patients who happen to have the germline BRCA1/2 mutations. There are actually additional treatment options for these patients if they have residual disease. And this was based on the OlympiA clinical trial. In this trial, men and women with germline BRCA1/2 mutations that were HER2 negative, who had completed definitive local therapy that include up to six cycles or more of a neoadjuvant, or adjuvant chemotherapy containing antracyclines and Oroxine regimen, they were split into two subgroups, triple-negative breast cancer or hormone receptor positive HER2 negative breast cancer and treated with Olaparib 300 milligrams BID for a year versus placebo.

Focusing on this group of patients, their primary endpoint was invasive disease-free survival. Their secondary endpoints was distant disease-free survival or overall survival. You can clearly see the three-year invasive disease-free survival was superior, 85.9% in Olaparib group and 77.1% in the placebo group. In terms of overall survival, there were 75 deaths in the Olaparib arm and 109 deaths in the placebo arm. And this was statistically significant improvement in both invasive disease free survival and overall survival in the Olaparib arm compared with placebo. So according to NCCN, one should consider the addition of adjuvant olaparib for one year, for those with germline BRCA1/2 mutations, particularly for those who have triple-negative breast cancer if they have pT2 or pN1 disease and above after adjuvant chemotherapy or residual disease, after pre-op chemotherapy.

Of notes, this patients in this trial did not receive capecitabine as we discussed in the previous slide, as per Create-X trial. Since they did not receive capecitabine, there is no data currently on sequencing guidelines of whether to give a PARP inhibitor olaparib prior to or after capecitabine, or use one agent over another. And at this time, this is left up to the physician clinical judgment and their own decision.

Special considerations to think about, especially when you using the keynote 522 regimen, because of the immunotherapy containing regimen with pembrolizumab, one has to monitor for immunotherapy related toxicities.

So during treatment you would monitor typically with typical CBC, CMP, but you will also wanna monitor for a thyroid panel with the TSH, T3, T4, and cortisol levels. You'll wanna monitor for immune-related AEs, like significant Rash, Colitis or Automimmune hepatitis, Hypo/hyperthyroidism, or symptoms of Adrenal Insufficiency. One would want to institute high dose steroids as soon as possible and any other therapy is indicated, and of course, discontinue immunotherapy if a high grade three or four IrAEs are observed. And it's important to note that this IrAEs may occur even months after therapy is completed. So the continued monitoring of this patient is important. We did know that it received immunotherapy and could be exhibiting signs of an immunotherapy related toxicity even months after therapy is completed.”