Revisit the Top 5 OncLive On Air Episodes of 2023

In case you missed it, below is a recap of the most popular episodes of OncLive On Air^® from 2023:

1) Breast Cancer Experts Review HR+ Treatment Updates From SABCS 2022

In exclusive interviews with OncLive^® during the 2022 San Antonio Breast Cancer Symposium, 5 breast cancer experts shared their insights on updates in the treatment of patients with hormone receptor (HR)–positive breast cancer.

Yen-Shun Lu, MD, PhD, of the National Taiwan University Hospital in Taipei, shared the primary results of the phase 2 RIGHT Choice trial (NCT03839823) evaluating ribociclib (Kisqali) plus endocrine therapy in premenopausal patients with aggressive HR-positive, HER2-negative breast cancer. “For patients who are intolerant to combination chemotherapy, ribociclib plus endocrine therapy [elicits] a greater response rate than single-agent chemotherapy,” Lu said. “But [even for patients who can tolerate combination chemotherapy], ribociclib plus endocrine therapy can provide a longer progression-free survival [PFS], lower toxicities, and better treatment compliance, which are all important for the success of treatments for our patients in critical situations.”

Patrick Neven, MD, PhD, of University Hospitals Leuven in Belgium, discussed findings from a pooled analysis of treatments after progression on frontline ribociclib and endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer who were enrolled in the phase 3 MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), and MONALEESA-7 (NCT02278120) trials. “Patients who initially start with endocrine treatment and the CDK4/6 inhibitor ribociclib [have] tumors that are not more aggressive, and there seems to be [a mechanism by which] these tumors remain endocrine sensitive, because if [patients have] a long duration on the combined treatment, you can still expect a long duration on subsequent endocrine treatment alone or in combination with a targeted treatment,” Neven explained.

William Jacot, MD, PhD, of the University of Montpellier in France, shared primary efficacy and safety findings from the phase 2 AMALEE trial (NCT03822468), which evaluated first-line ribociclib starting doses of 400 mg and 600 mg in HR-positive, HER2-negative advanced breast cancer. “[It is] quite reassuring for clinical practice to say that in case of toxicity, it doesn’t look like we are losing chances to reduce the dose [of ribociclib], and [in so doing], we will alleviate part of the toxicity effects,” Jacot emphasized.

Arielle Medford, MD, formerly a clinical fellow in medicine at Dana-Farber Cancer Institute in Boston, Massachusetts, currently of Massachusetts General Hospital in Boston, walked through findings with cell-free DNA monitoring from the phase 2 LEADER trial (NCT03285412), which is evaluating the addition of ribociclib to adjuvant endocrine therapy in patients with localized HR-positive, HER2-negative breast cancer. “Of the 42 [evaluable] patients, only 2 had positive circulating tumor DNA (ctDNA), so evidence of minimal residual disease, and at the time of follow-up, those were the only 2 patients who had metastatic recurrences,” Medford stated. “Meanwhile, 40 other patients had multiple tests for ctDNA, all of which were negative, and at the time of follow-up, none of those patients had experienced recurrence.”

Laura Spring, MD, of Massachusetts General Hospital Cancer Center, discussed findings from an analysis of the phase 3 RxPONDER trial (NCT01272037), which evaluated the effect of HER2-low status on clinical outcomes in patients with HR-positive, HER2-negative breast cancer who received endocrine therapy alone or with chemotherapy. “Pathology is going to play a major role here,” Spring emphasized. “Now that we have agents approved in the advanced breast cancer setting, it’s going to be important for accurate HER2 testing.”

2) Breast Cancer Experts Review 2023 MBCC Research Updates and the Importance of Multidisciplinary Collaboration

In exclusive interviews with OncLive conducted during the 40th Annual Miami Breast Cancer Conference^®, 6 experts in breast cancer care discussed treatment advances and important regulatory decisions for patients with breast cancer.

Patrick Borgen, MD, of Maimonides Medical Center in Brooklyn, New York, as well as the chair of the Miami Breast Cancer Conference^®, discussed the importance of holding such multidisciplinary conferences for clinicians. “At the core of [this meeting] is our faculty,” Borgen emphasized. “Choosing faculty, matching them with topics they’re passionate about, finding faculty who are good communicators, good educators, who are approachable, who embrace our audience, is the art to this meeting.”

Laura J. Esserman, MD, MBA, of the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, as well as the 2018 Giants of Cancer Care^® award winner for cancer diagnostics, shared future directions for the phase 2 I-SPY 2 trial (NCT01042379) in patients with high-risk breast cancer and the importance of considering early end points in clinical trials. “The identification of early end points has enabled us to tailor treatment in a different way to understand the biology of breast cancer better, to improve the way we classify tumors, to drive response rates up over the course of the past decade,” Esserman noted. “The future is about tailoring care, less for the great responders, more a goal for the patients who are not having optimal responses.”

Kelly K. Hunt, MD, FACS, FSSO, of The University of Texas MD Anderson Cancer Center in Houston, talked through considerations for axillary reverse mapping in breast cancer for the reduction or prevention of lymphedema. “The best role for axillary reverse mapping is to use it at the same time that you’re doing axillary lymph node dissection,” Hunt said. “[Axillary reverse mapping] prevents lymphedema, and so doing it upfront, rather than waiting for the patient to get lymphedema and then trying to do corrective surgery…doesn’t work as well.”

Kevin Kalinsky, MD, MS, of the Winship Cancer Institute of Emory University in Atlanta, Georgia, shared best practices for sequencing antibody-drug conjugates (ADCs) for patients with triple-negative breast cancer (TNBC). “Sacituzumab govitecan-hziy [Trodelvy] was approved and showed an overall survival benefit specifically in patients with TNBC.” Kalinsky postulated. “[Sacituzumab govitecan] tends to be the preferred initial ADC.”

Lisa A. Carey MD, ScM, FASCO, of the University of North Carolina Lineberger Comprehensive Cancer Center, discussed the use of response-guided therapy in nonmetastatic HER2-positive breast cancer. “We can minimize surgery through neoadjuvant therapy,” Carey stated. “We can tailor the use of more aggressive drugs, such as trastuzumab emtansine, predicated on [whether patients] have residual disease.”

Steven J. Chmura, MD, PhD, of the University of Chicago Comprehensive Cancer Center in Illinois, highlighted oligometastatic breast cancer management. “[The phase 2/3 NRG-BR002 trial (NCT02364557)] was the first trial to test the hypothesis: Could local intervention help?” Chmura said. “It has been 25 years, and we have a lot of data, publications, and hopes, but what…impact does local therapy have, and what do the results of the NRG-BR002 trial, which is a negative trial, inform for us going forward? Is there a path to go forward in terms of these local interventions?”

3) FDA Approval Insights: Elacestrant in ER+/HER2- ESR1-Mutated Advanced or Metastatic Breast Cancer

In January 2023, the FDA approved elacestrant for postmenopausal women and adult men with estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who have progressed on 1 or more lines of endocrine therapy. The regulatory decision was supported by the results of the phase 3 EMERALD trial (NCT03778931), in which patients who received elacestrant achieved a median PFS of 3.8 months (95% CI, 2.2-7.3) vs 1.9 months (95% CI, 1.9-2.1) with control endocrine therapy.

In an exclusive interview with OncLive, Francois-Clement Bidard, MD, PhD, of the Institut Curie and Université Paris-Saclay in France, spotlighted the significance of this approval, key findings from EMERALD, and why it is important to test for ESR1 mutations in patients with ER-positive, HER2-negative disease. “[Elacestrant] is the first drug in a new class, the oral selective estrogen receptor degraders,” Bidard explained. “With this approval, now we know that these drugs can make it to patients. It’s a significant signal that we can increase the efficacy of endocrine therapy.”

4) FDA Approval Insights: Enfortumab Vedotin Plus Pembrolizumab in Urothelial Carcinoma

In April 2023, the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) received accelerated FDA approval for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This approval was supported by data from the dose-escalation, A, and K cohorts of the phase 1/2 EV-103/KEYNOTE-869 trial (NCT03288545). In these cohorts, treatment with the combination led to a confirmed objective response rate of 68% (95% CI, 59%-76%). In December 2023, this combination received full FDA approval for patients in this population.

In an exclusive interview with OncLive, Terence Friedlander, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, highlighted the significance of the accelerated approval, top findings from EV-103, and how these data support the incorporation of such an active first-line combination regimen for patients in this population. “We’re seeing a consistent signal when we add enfortumab vedotin and pembrolizumab together in the front line,” Friedlander emphasized. “That’s exciting, and it means that patients will respond. This was traditionally a poor prognosis group that had limited options, so [this approval] is a real step forward for the field.”

5) FDA Approval Insights: Zanubrutinib in CLL and SLL

In January 2023, the FDA approved zanubrutinib (Brukinsa) for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This regulatory decision was backed by data from the phase 3 SEQUOIA trial (NCT03336333) in patients with treatment-naïve disease and data from the phase 3 ALPINE trial (NCT03734016) in patients with relapsed/refractory disease. In SEQUOIA, treatment with zanubrutinib led to a median PFS that was not reached (NR) vs 33.7 months with bendamustine and rituximab (Rituxan; BR) in a randomized cohort. In ALPINE, the median PFS was NR in patients who received zanubrutinib vs 34.2 months in those treated with ibrutinib (Imbruvica).

In exclusive interviews with OncLive, 4 lymphoma experts shared their insights regarding the approval. Ian W. Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, Tennessee, discussed the significance of this approval. “The approval of zanubrutinib for CLL and SLL is important because it allows another option for patients in the frontline and relapsed settings,” Flinn emphasized. “There are several other treatment options for patients, but the safety and efficacy profile of this drug is important for patients with these diseases.”

Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, and Constantine Tam, MD, MBBS, of Alfred Health in Melbourne, Australia, share efficacy and safety data from the pivotal trials. “[In ALPINE], zanubrutinib significantly improved PFS compared with ibrutinib by [12.5%] at [29.6] months of follow-up,” Brown explained. “This effect was even greater in the highest-risk [population of] patients [with 17p deletions and/or TP53 mutations], at [18%], which indicates that there’s a real biologic phenomenon going on with zanubrutinib being more effective, perhaps related to the maintenance of drug levels throughout the dosing interval.”

“Grade 3/4 neutropenia is higher with zanubrutinib compared with ibrutinib, but that’s the only toxicity that is disadvantageous for zanubrutinib,” Tam noted. “That neutropenia does not translate to increased infections…. In my practice, the neutropenia is not dose-limiting…and in my experience, most of these [cases of] neutropenia resolve after a few weeks.”

Finally, Nicole Lamanna, MD, of the Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York, noted the mechanism of action of zanubrutinib and its role in the CLL/SLL treatment paradigm. “I think we’re going to see an increase in usage of zanubrutinib, not only as monotherapy, but from combination studies [investigating regimens] such as zanubrutinib plus venetoclax. It’s going to be an exciting time to see more longer-term follow-up in the [SEQUOIA and ALPINE] studies, but also in the combination studies with zanubrutinib, increasing the frequency of its usage, both in the frontline and relapsed settings.”