Advertisement


Ann H. Partridge, MD, MPH, and Véronique Diéras, MD, on the Future of Cytotoxic Therapy: Antibody-Drug Conjugates?

2022 ASCO Annual Meeting

Advertisement

Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, and Véronique Diéras, MD, of the Centre Eugène Marquis, discuss the many challenges posed by next-generation antibody-drug conjugates (ADCs). They include side effects such as hematotoxicity, gastrointestinal toxicities, and interstitial lung disease; tumor targeting and payload release; drug resistance; and the urgent need to understand ADCs’ mechanisms of action to better sequence and combine drugs.



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Ann H. Partridge: Veronique, it's been a pretty exciting ASCO to be a breast cancer doctor and researcher. Tell me about these new drugs, the antibody conjugates that are making such a splash. Véronique Diéras: Yes. And in fact, it took more than a century to have this targeted chemotherapy in order to improve the therapeutic index of cytotoxic chemotherapy. We were using TDM-1 for many years, but the third generation of ADC have some particular and mainly the bystander effect what we call. So there is a release of the cytotoxic, the payload of the antibody in the micro environment, leading to activity in tumor cells that might not express the target of the ADC. So the bystander effect may increase the efficacy of the ADC, but also perhaps the toxicity. Ann H. Partridge: So it allows for that tumor heterogeneity that we're learning so much about to be targeted? Véronique Diéras: Yes, exactly. Tumor heterogeneity and moreover targeting tumor cells with low expression. We know, for instance, with the anti-ER therapy, it was active only in case of early to free expression, like for TDM-1 trastuzumab. And then with this new ADC and the bystander effect, there may be some activity on HE. Ann H. Partridge: R2 low expression, breast cancer. Ann H. Partridge: Yeah, and what do you mean by activity? What have we seen both in your work and what we saw here at ASCA? Véronique Diéras: Trastuzumab deruxtecan was very active in HER positive breast, metastatic breast cancer, according to the [inaudible] breast of free. But at this ASCO, we heard about the activity in HER2 low breast cancer. We have already refuted data from the early clinical trials, but we have the release of destiny breast or four comparing Trastuzumab deruxtecan versus chemotherapy choice of the physician. In every treated patient mainly ER positive too low, but some were negative. And clearly the results were impressive with a superiority, not only in probation free survival, but in response rate and interval survival. That means a lot for our patient because I think there will be a major impact for two mobile in our clinical practice. Ann H. Partridge: Right. And it worked in all subsets. Right? Véronique Diéras: Exactly. Ann H. Partridge: All subtypes. Yeah. If they express some HER2, right? Véronique Diéras: Yes. HER2 low, even if it's ER negative. So what we may call triple negative by the definition of today, we may have some activity too. Ann H. Partridge: That's right. About 30% express some HER2 correct? Véronique Diéras: Yes. Ann H. Partridge: Something like that. And what about the tolerability of these drugs? What are we learning? Véronique Diéras: There's no new safety signals from what we know from destiny breast free, it was an update of the safety during this meeting too. But perhaps we have to be cautious about interstitial lung disease, ILD, but in fact the incidence on the severity of ILD decrease with the implementation of guidelines and perhaps more over treating less pretreated population. Ann H. Partridge: So now we have a number of monoclonal antibody, conjugate drugs, where do we go from here? Where do we need to go research wise and what can we do on Monday in the clinic? Véronique Diéras: So on Monday in the clinic, we may use precision risk account, but in fact, we have many ADC with different target from HER2 low from HER3 and from [inaudible]. Véronique Diéras: And we have activity, I think HER3, we have as a preliminary development, but it's very exciting data. We have from the phase one and two study, but for tomorrow, what we need to know the best, we will address this ADC on the sequencing, the choice of the ADC for each patient. So today we say, considering the result we have with Trastuzumab [inaudible] HER2 low, ER positive, I will say the best choice will be Trastuzumab deruxtecan because we have an impact on world survival, but we may have activity with Trop2 ADC. So we have for the next future to evaluate the sequencing of this ADC, to evaluate the mechanism of resistance, because it'll have an important value to set the sequence. And also perhaps combination because we know from cyto toxic chemotherapy. When we combine with other drug immune checkpoint inhibitor, PAP inhibitor, sometimes we may have increase of activity. So we have a lot. I think it's the beginning of the story of it, in fact. Ann H. Partridge: So the beginning, and wouldn't it be nice if we could have a cocktail and then move it into the earlier stage setting and effect more cures? Véronique Diéras: Yes. Ann H. Partridge: That's what we want to see ultimately. Véronique Diéras: Yes, exactly. I was thinking of that, looking to the result of this of study of four. When I see the response rate in every pre-treated population. What may be the impact for instance, in the new adjuvant setting for ER positive, HER2 low, because we know usually the PCR is very low in ER positive diseases. So perhaps we have to evaluate Trastuzumab in the adjuvant setting to increase the PCR to have an impact on the cure of the patient. Ann H. Partridge: All right. I heard it here. I think that's the future. Thank you so much Veronique for joining me. Véronique Diéras: Thank you.

Related Videos

Breast Cancer

Stephanie Walker on Increasing the Participation of Black Women With Metastatic Breast Cancer in Clinical Trials

Stephanie Walker, a former nurse and current activist with the Metastatic Breast Cancer Alliance, discusses findings from the BECOME project (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement). They show that, even though Black patients comprise between 4% and 6% of all clinical trial participants, Black women with metastatic breast cancer are willing to consider taking part if steps were taken to increase their awareness, build trust through clear communication with health-care providers, involve people of shared racial/ethnic identity and health experience, and help patients find and access trials (Abstract 1014).

Breast Cancer
Immunotherapy

Erika Hamilton, MD, on Metastatic Breast Cancer: Safety Follow-up Data on T-DXd vs T-DM1

Erika Hamilton, MD, of Sarah Cannon Research Institute at Tennessee Oncology, discusses phase III data from the DESTINY-Breast03 study, which reinforced the consistent safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd) vs ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer. The findings also support T-DXd’s risk benefit over that of T-DM1 (Abstract 1000).

Issues in Oncology
Global Cancer Care

Clifford A. Hudis, MD, and Karen E. Knudsen, PhD, MBA, on How ASCO and the American Cancer Society Are Collaborating to Help Patients With Cancer

Clifford A. Hudis, MD, of the American Society of Clinical Oncology, and Karen E. Knudsen, PhD, MBA, of the American Cancer Society, discuss their collaboration, pooling their research and education resources to help empower patients with cancer and their families. Within 48 hours, Drs. Hudis and Knudsen were able to gear up a rapid response to the crisis in Ukraine, forming a clinical corps of volunteers to post information online in multiple languages, which helped patients navigate their care in the war-torn region. To date, 300 European cancer organizations have joined their efforts.

Prostate Cancer
Genomics/Genetics

Neal D. Shore, MD, on Germline Genetic Testing and Its Impact on Prostate Cancer Clinical Decision-Making

Neal D. Shore, MD, of the Carolina Urologic Research Center, discusses his study findings, showing that germline genetic testing influenced care for patients with prostate cancer. Men whose genetic test was positive for a pathogenic germline variant received more recommendations for changes to follow-up and treatment, and for testing and counseling of relatives, than did patients with negative or uncertain test results (Abstract 10500).

 

Breast Cancer

Tara B. Sanft, MD, on How Diet and Exercise May Affect Completion of Chemotherapy for Breast Cancer

Tara B. Sanft, MD, of Yale University, discusses the results of the LEANer study (Lifestyle, Exercise, and Nutrition Early After Diagnosis) in women with breast cancer. It showed that patients with newly diagnosed disease who were just starting chemotherapy could improve physical activity and diet quality. While both groups had high rates of treatment completion, women in the intervention who exercised at or above the recommended levels did better in terms of treatment completion, with fewer dose reductions and delays (Abstract 12007).

 

Advertisement

Advertisement




Advertisement