Part 2: Experiences With Sacituzumab and Biomarkers for TNBC

Joyce O’Shaughnessy (Moderator)

Co-Chair of Breast Cancer Research

Chair of Breast Cancer Prevention Research

Baylor-Sammons Cancer Center

Dallas, Texas

DISCUSSION QUESTIONS:

• What are your experiences with the efficacy and toxicity of sacituzumab govitecan (Trodelvy)? What is your approach to monitoring and management?
• How do you counsel your patients regarding sacituzumab govitecan, including mechanism of action and toxicity?

JOYCE O'SHAUGHNESSY, MD: What do you say to your patients with regard to sacituzumab? Who has used it here?

ASHWANI K. AGARWAL, MD: I have used it in 2 patients, and with 1 of the patients I had to fight with the insurance companies. Finally, they did approve it. The response rate was good, but the biggest challenge was neutropenia. You have to use growth factors. They will not approve pegfilgrastim [Neulasta] so I used GCSF [granulocyte colony-stimulating factor], but this patient was already bald, so he did not care about the hair loss. It was fairly well tolerated otherwise; not many adverse events [AEs] except for neutropenia.

THOMAS W. FROEHLICH, MD: I have used sacituzumab in several patients and had pretty good responses. One of them was not very durable. I just saw a patient the other day who is on it for bone metastasis only, and I am curious because she has only had a few doses. Does anyone else have experience in triple-negative breast cancer [TNBC] where the patient has bone-only metastasis who knows what the responses will be? I do not know if that is different than visceral metastasis.

O'SHAUGHNESSY: I cannot recall a bone-only patient, but I participated in a phase 2 study in the estrogen receptor [ER]–positive, HER2-negative population, and it is not uncommon to see patients with only bone metastases. I had patients with bone metastases only, ER-positive, HER2-negative breast cancer that did well. So I think this is a drug that was helpful for TNBC, I think it is helpful for luminal breast cancers as well. So I did not have any specific TNBC bone-only [patients on] this drug, but I did with the ER-positive [patients], so I suspect it could be useful for them too.

AGARWAL: Is it approved for ER-positive [disease] yet?

O'SHAUGHNESSY: No, we are waiting on the phase 3 trial results. We do not have accelerated approval. The phase 3 trial is completed. It is called the TROPiCS-02 trial [NCT03901339]. We’re waiting on the phase 3 data for approval. So we cannot get this drug for patients who are ER positive yet unfortunately.

AGARWAL: Because I do have a patient who needs it.

O'SHAUGHNESSY: You should biopsy her again. Maybe the cancer will come back ER negative. The only thing we can do is hope that the cancer has lost the ER status, which they tend to do in the liver. Androgen receptor status comes up to take over.

ALLISON E. GORREBEECK, MD: I had one patient that just started on it. So far, so good. Her biggest issue so far has been a little bit of nausea. She is not far enough along yet for me to assess for response though. It is manageable nausea, but that has been her biggest complaint.

O'SHAUGHNESSY: I find that they need a good intravenous antiemetic regimen. I find it effective if you have a good-quality regimen, even if it is only given on day 1 and day 8.

DISCUSSION QUESTIONS:

• What is your overall approach to molecular testing at metastatic relapse/progression?
• Have we learned anything about the value of potential biomarkers to guide use of this agent (eg, Trop-2 expression, germline BRCA1/2 mutation status)?

O’SHAUGHNESSY: I would be curious to see what people do for molecular testing. PD-L1, germline BRCA, Trop-2. I do not think we need the Trop-2, and 1 of the therapies in the comparator arm they received that we already mentioned what those were. What do people get for testing as a newly diagnosed patient? I am just curious in the metastatic setting in terms of biomarker studies.

ANDREW KOVOOR, MD: I have to check my PD-L1 if it is positive then you can give atezolizumab [Tecentriq] and nab-paclitaxel [Abraxane]. If it is negative, I will usually just use a Taxol.

O'SHAUGHNESSY: Yes. And germline BRCA?

KOVOOR: Yes, I will check that as well.

O'SHAUGHNESSY: But you don’t see a particular role for next-generation sequencing [NGS] or circulating tumor DNA [ctDNA] analysis?

KOVOOR: Now I do not know much about the ctDNA. I have been getting a lot of pushback now from the insurance companies on breast cancer and checking NGS. They told me they only need the PD-L1 and BRCA testing and ask why I want more.

O'SHAUGHNESSY: I think with pembrolizumab being approved for microsatellite instability–high, that is one justification for giving it with a tumor mutational burden [TMB] 10 mutations per megabase or higher.¹ I think with TMB 10 or higher, there are data from the KEYNOTE-119 trial [NCT02555657] of pembrolizumab, the high TMB also predicts benefit for single-agent pembrolizumab.² If we found NTRK fusions, we could certainly use entrectinib [Rozlytrek] or one of the other NTRK inhibitors because they are approved as tumor agnostics if fusions are found in one of the NTRK genes.^3,4 So there are a few things we could do. The list is not very long before considering clinical trials. I have a patient right now who I sent over to Dr Nisha Unni at the University of Texas Southwestern Medical Center. She is participating in a trial [NCT04024436] of an oral FGFR1 inhibitor [futibatinib] and [fulvestrant (Faslodex)]. I think it is helpful there, but there are a few things I think we could justify to the insurance company because they are approved as tumor agnostic.

FROEHLICH: We test for FGFR because of the FGFR trial at the University of Texas Southwestern Medical Center.

O'SHAUGHNESSY: Yes. I had a remarkable response [in a patient with TNBC]. She [had] germline BRCA1, and she had responded to a PARP inhibitor. Then she did not respond to anything I gave her after the PARP inhibitor. The cancer was growing out of her neck. She had a huge adenopathy threatening her airway. At the time of the trial [NCT02052778] for the Taiho Pharmaceutical drug called TAS-120 [or futibatinib], and she went over to Mary Crowley Cancer Research Center and got this drug, and overnight, that adenopathy was gone. She had a high level of FGFR2 amplification. The response was durable, too, so I am hoping that is going to end up being a drug for these patients. So that trial is available at University of Texas for FGFR1.

JAGATHI CHALLAGALLA, MD: Is it specific to FGFR1, or for FGFR 1, 2, or 3?

O'SHAUGHNESSY: It targets FGFR 1, 2, and 3. In the trial for TNBC, the patients must have FGFR2 amplification. It may be open for the FGFR1 amplification and ER positive, but this patient I sent over there has TNBC, but it is an interesting drug. So we certainly need a blocker for FGFR. I get NGS on these patients because I can sometimes find a biomarker that would make a patient eligible for a clinical trial.

_References:

_{1. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. FDA. May 23, 2017. Accessed December 21, 2021. https://bit.ly/3yRWs91}

_{2. Winer EP, Lipatov O, Im SA, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499-511. doi:10.1016/S1470-2045(20)30754-3}

_{3. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. FDA. August 15, 2019. Accessed December 21, 2021. https://bit.ly/3so2EnY}

_{4. FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA. November 26, 2018. Accessed December 21, 2021. https://bit.ly/3sm18CZ}