By Abigail Johnston
Disclaimer: This post is not intended to be taken or received as medical advice nor is the author able to offer medical advice. Each patient who is interested in medication or statements made herein should consult with a qualified medical professional to learn more.
Trodelvy Approval
On April 22, 2020, the FDA approved sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease, so it would be the third line of treatment for those living with mTNBC. Trodelvy (try saying that 5 times fast) is the first antibody-drug conjugate approved by the FDA specifically for metastatic triple-negative metastatic breast cancer. It is also the first FDA-approved anti–Trop-2 antibody-drug conjugate. If that sounds like another language, it really is. The bottom line is that this new medication represents a significant step forward in the treatment of mTNBC, a diagnosis that often carries a very grim prognosis and, until recently, has lagged behind the other subtypes in terms of available treatments outside of traditional chemotherapy.
As of December 2020, Gilead released new data from the ASCENT trial that continues to show promising results of Trodelvy for patients with mTNBC. Gilead has submitted a Biologics License Application (sBLA) to the Food and Drug Administration (FDA) to receive full approval for Trodelvy as a treatment option for adult patients with mTNBC who have received at least two prior therapies.
Trodelvy and Metastatic Triple-Negative Breast Cancer
“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. The approval of sacituzumab govitecan-hziy represents a new targeted therapy for patients living with this aggressive malignancy,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “There is intense interest in finding new medications to help treat metastatic triple-negative breast cancer. [This] approval provides patients who’ve already tried two prior therapies with a new option.” For more information from ASCO (American Society of Clinical Oncologists), you can read more here.
ASCENT Trial
The trial (ASCENT) that led to the approval by the FDA in May of 2020 enrolled 108 patients (a BIG thank you to those brave souls) who had undergone a range of 2-10 prior treatments for metastatic disease. The medication (10mg/kg) is an injection administered twice in a 21-day period. From my review of the study, “The overall response rate was 33.3% (95% confidence interval [CI] = 24.6%–43.1%), with a median duration of response of 7.7 months (95% CI = 4.9–10.8). Of the patients with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for 6 or more months and 16.7% maintained their response for 12 or more months.”
Trodelvy Side Effects
The side effects are pretty similar to many other targeted therapy with 25% or more reporting nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash, and abdominal pain. The worst side effects, which are included in the boxed warning are the risks for severe neutropenia and severe diarrhea.
The confirmatory phase III ASCENT study was recently halted by the independent data safety monitoring committee because of the data that was already collected in light how well the Trodelvy appears to be working; however, access to Trodelvy may be contingent on the ASCENT study continuing to show the same data. This is an example of expedited approval prior to the conclusion of Phase III (the last phase) of the trial and represents the FDA’s commitment to expediting the approval process of medication that shows efficacy to the public. Ongoing monitoring of safety and the experiences of patients on the medication will be key to watch as more men and women are prescribed the medication and more endpoints are reviewed.
One aspect of trials conducted in the US under the supervision of the FDA are those endpoints. Most trials look at Progression Free Survival (PFS), as was examined in ASCENT for Trodelvy. It could certainly be argued that having the approval expedited prior to the end of Phase III of the trial means we are missing key data. We are missing the Overall Survival (OS) data that patients are often very concerned about. At the same time, the medical professionals involved with the trial and the approval process deemed that patients having access to the medication in light of its niche and being the first in its class was more important than waiting on that data. The patients taking the medication as a last resort are certainly happy about that.
Listen to our latest podcast featuring a lively discussion on Trodelvy and treatment options for metastatic breast cancer.
For more information on TNBC, read an interview with Sara and Caitlin, two thrivers of SBC's community, here.
About the Author:
In 2017, at the ripe old age of 38, while living in Orlando, Florida, I was diagnosed with Stage IV Metastatic Breast Cancer after feeling a lump in my left breast while tandem nursing my boys, who are now 7 and 5. The summer of 2017 was a rollercoaster of emotions as I faced four body and life changing surgeries amidst chemo and radiation. Once the whirlwind had settled a bit and I’d completed transitioning my clients and staff at my law firm to another law firm, my husband, two boys and I moved to Miami to live with my family. Looking back, I’m astonished at how much has changed, how much we have overcome as a family, and how everyone has adjusted. While I don’t actively practice law, I use my education and training in a variety of ways for the breast cancer community, advocating for patients and thrivers. I have started my own non-profit, Connect IV Legal Services, where I recruit lawyers to do pro bono work for Stage IV patients. I’m also active in many local and national organizations, volunteering and adding my voice to educate and persuade others to connect with and help my community. You can connect with me by checking out my blog, www.NoHalfMeasures.blog, or following me on Twitter, Instagram, Facebook, LinkedIn, or YouTube! - Abigail Johnston
