ASCO 2022 | ADCs for the treatment of HER2-low breast cancer
Paolo Tarantino, MD, Dana-Farber Cancer Institute, Boston, MA, reflects on the use of antibody-drug conjugates (ADCs) for the treatment of HER2-low breast cancer, including trastuzumab duocarmazine which was evaluated in the TULIP trial (NCT03262935), where it demonstrated activity in HER2-low patients, as well as disitamab vedotin which has shown similar response rates. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Transcript (edited for clarity)
So, we’re very curious to discover if we can use different antibody-drug conjugates in serious, in the same patient, and we don’t know if this is going to be possible. Now, we know that trastuzumab deruxtecan is going to enter the practice, but it’s not the only ADC that has strong activity in HER2-low disease. We have at least two more. The first one actually was published was trastuzumab duocarmazine, which is also a potent novel anti-HER2 antibody-drug conjugate, which has positive phase 3 data in HER2-positive disease, the TULIP trial, but actually showed also around 30 to 40% response rate in HER2-low disease...
So, we’re very curious to discover if we can use different antibody-drug conjugates in serious, in the same patient, and we don’t know if this is going to be possible. Now, we know that trastuzumab deruxtecan is going to enter the practice, but it’s not the only ADC that has strong activity in HER2-low disease. We have at least two more. The first one actually was published was trastuzumab duocarmazine, which is also a potent novel anti-HER2 antibody-drug conjugate, which has positive phase 3 data in HER2-positive disease, the TULIP trial, but actually showed also around 30 to 40% response rate in HER2-low disease. A few patients, less than 50 patients were treated, but it’s still telling us that this drug is interesting for the HER2-low space. And another interesting drug is called brentuximab vedotin and this drug also has shown around 30 to 40% response rate in HER2-low.
These responses in phase 1 trials appear to be shorter lived compared to Trastuzumab deruxtecan. Trastuzumab deruxtecan had a median PFS of 11 months in the phase 1, and around 10 months in the phase 3 that we have seen today. Whereas, these drugs have around five months of PFS, four to five months, so we are not sure if we are going to see this benefit also in larger studies. However, I really think that there might be a place for more ADCs, and this is also why we really need to study the resistance mechanism to this novel ADCs.
We are working on profiling the biopsies of patients treated with Trastuzumab deruxtecan, T-DM1 and other ADCs to really understand what happens when the patient progress. And it is going to be important both for HER2-positive disease, but also for HER2-negative or HER2-low disease. Because, apart from HER2-positive, Anti-HER2 ADCs, we have so many other ADCs coming. We have Anti-TROP2 antibodies like the Datopotamab Deruxtecan, Sacituzumab Govitecan, we have Patritumab Deruxtecan that was also shown to have a high response rate in breast cancer. So, in the future, we are going to need to understand if we can sequence these drugs, what is the best sequence of this drug? And to do this, we need to study the mechanism or resistance, and understand what happens when the patient progress to these treatments.
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