Part 1: Frontline Therapy Options for Rapid Recurrence in Metastatic TNBC

Joyce O’Shaughnessy (Moderator)

Co-Chair of Breast Cancer Research

Chair of Breast Cancer Prevention Research

Baylor-Sammons Cancer Center

Dallas, Texas

CASE SUMMARY:

A 48-year-old woman with T1N1 triple-negative breast cancer (TNBC) received adjuvant dose-dense doxorubicin (Adriamycin), cyclophosphamide (Cytoxan) and paclitaxel (Taxol), which she tolerated well. Eight months after completion of adjuvant therapy, she reported worsening fatigue. ​Lab tests showed alanine aminotransferase 1.5 times the upper limit of normal and aspartate aminotransferase 1.5 times above the upper limit of normal levels. ​A CT scan showed 1 liver and 2 left lung lesions​. A biopsy of the liver lesion confirmed recurrent metastatic TNBC.

A brain MRI was negative for brain metastasis. Genetic panel testing was negative for detectable mutations​. The PD-L1 level on immune cells from a SP142 Ventana assay was 0%​. The patient had no significant comorbidities and was otherwise healthy​. She had an ECOG performance score of 0.

The patient recurred 8 months after receiving adjuvant therapy. She received front-line gemcitabine (Gemzar)/carboplatin with a documented partial response lasting 6 months, but after 6 months of therapy, she reported worsening fatigue. Disease progression and new metastasis in the liver were discovered, and the patient’s ECOG performance score was 1.

DISCUSSION QUESTIONS:

• Which therapeutic options for this patient with rapid recurrence would you seriously consider?
• Which one are you most likely to recommend and why?
• What do you consider the ideal therapeutic sequence for PD-L1–negative, BRCA-negative metastatic TNBC?

JOYCE O’SHAUGHNESSY, MD: What would you do in the first and second-line setting for this very rapidly recurring patient?

DILIP SOLANKI, MD: I would probably choose carboplatin/gemcitabine just to give her something new. She is young enough and her ECOG performance score is still good at 1. That would be my choice in her case. I always have reservations about giving platinum to patients, but I remember your study with carboplatin/gemcitabine when we did the PARP study with good response, so that would be my choice, and I would use combination chemotherapy because of the aggressive nature of the disease and visceral disease.

JAGATHI CHALLAGALLA, MD: I would probably include a platinum agent too. I would give carboplatin/gemcitabine. This patient is progressing very rapidly. For single-agent NCCN [National Comprehensive Cancer Network] guidelines, I think I would go with carboplatin/gemcitabine.

O'SHAUGHNESSY: Yes, that is one where you make an exception and do a combination. There seems to be some acceptance here of a gemcitabine/carboplatin-type approach. What would people give as a second-line treatment in this rapidly recurring patient?

CHALLAGALLA: In the way that sacituzumab [Trodelvy] is approved, you should have at least 2 lines of therapy with at least one in the metastatic setting.¹ So, if you already got carboplatin/gemcitabine in the metastatic setting, I would go for sacituzumab instead of eribulin [Halaven].

O'SHAUGHNESSY: Yes. I think that is one of the main messages of this case for oncologists that may not be aware of this. You could get on the ASCENT trial [NCT02574455] if you had just 1 regimen in the metastatic setting, if you had a treatment-free interval of less than a year. They counted adjuvant therapy or neoadjuvant therapy as a regimen if you recurred very quickly, and so it is on the FDA label, and it is acceptable to give the sacituzumab in 1 of these patients that has very bad disease.¹ We do it in the second line if the treatment-free interval was less than a year. That is actually 1 of the main points of this, but not every single patient needs to get a third-line treatment before sacituzumab.

SOLANKI: They had to have a taxane before. That was another requirement.

O'SHAUGHNESSY: I think that is right that they had to have taxane at some point. Are there any other comments that people want to make so far about this case?

ROBYN YOUNG, MD: I would almost think of this patient’s adjuvant doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as her first-line therapy because she recurred so rapidly. You would consider that her first-line treatment and you give gemcitabine/carboplatin second. Sacituzumab would be the third-line therapy.

O'SHAUGHNESSY: Exactly, and I think that is what the FDA agreed to. I think they completely agree that it counts as first-line treatment. I mean, the patient received it so recently.

BRAMHAM A. REDDY, MD: Dr O'Shaughnessy, could you comment as to what percentage of the patients who received sacituzumab received a platinum agent as a prior chemotherapy?

O'SHAUGHNESSY: I think in the ASCENT trial it was a good, high number, because the patients in the ASCENT trial were getting a median of 3 prior lines of therapy.² So they were heavily pretreated. I think most of the patients had a prior platinum, and that is an important question because we are using platinum more and more in the curative setting, and now that we have pembrolizumab [Keytruda], the checkpoint inhibitor, approved to be given preoperatively that is with the platinum regimen.³ Of course, we all know that is paclitaxel-carboplatin followed by doxorubicin hydrochloride and cyclophosphamide. So many of our patients now are going to have platinum. It is an important question, how well the sacituzumab will do after a platinum-based agent.

_References:

_{1. Trodelvy (sacituzumab govitecan-hziy). Prescribing information. Immunomedics, Inc; 2021. Accessed December 21, 2021. https://bit.ly/3edFXKX}

_{2. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485}

_{3. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. FDA. July 26, 2021. Accessed December 21, 2021. https://bit.ly/3sqMn1O}