Oncology On The Go CancerNetwork

Experts discuss updated findings presented at the 2024 EHA Congress in diseases such as mantle cell lymphoma and acute myeloid leukemia.

Following the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Neil M. Iyengar, MD, and Paolo Tarantino, MD, co-hosted a live X Space with CancerNetwork® and discussed the latest trial updates that may impact clinical practice in the breast cancer field.





Iyengar is an associate attending physician at Memorial Sloan Kettering Cancer Center and a co-editor-in-chief of ONCOLOGY®. Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School. 





Iyengar and Tarantino discussed data regarding several trials and studies presented at the meeting. These presentations included: 





·      Phase 3 DESTINY-Breast06 Trial (NCT04494425)1

o   Investigators evaluated treatment with trastuzumab deruxtecan (T-DXd; Enhertu) compared with investigator’s choice of chemotherapy among patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer.

o   The median progression-free survival (PFS) was 13.2 months with T-DXd compared with 8.1 months in patients who received chemotherapy across the HER2-low population (HR, 0.62; 95% CI, 0.51-0.74; P .0001).

o   Primary analysis overall survival (OS) data show favorable trends in the T-DXd arm across the HER2-low group (HR, 0.83; 95% CI, 0.66-1.05; P = .1181) and the intent-to-treat (ITT) population (HR, 0.81; 95% CI, 0.65-1.00). However, the OS data only reached 40% maturity at the time of the analysis.

·      Phase 3 postMONARCH Study (NCT05169567)2

o   Patients with HR-positive, HER2-negative breast cancer and disease progression on CDK4/6 inhibitors and endocrine therapy were assigned to receive abemaciclib (Verzenio) or matched placebo plus fulvestrant (Faslodex).

o   The median PFS per investigator assessment was 5.6 months (95% CI, 5.4-9.2) with abemaciclib-based therapy vs 3.9 months (95% CI, 3.7-5.4) with placebo plus fulvestrant (HR, 0.66; 95% CI, 0.48-0.91; P = .01). 

o   The investigator-assessed objective response rate (ORR) was 17% vs 7% in each respective arm.

·      Phase 2 SACI-IO HR+ Trial (NCT04448886)3

o   Investigators assessed sacituzumab govitecan-hziy (Trodelvy) alone or in combination with pembrolizumab (Keytruda) for HR-positive, HER2-negative metastatic breast cancer regardless of PD-L1 status.

o   Combination therapy yielded a numerical improvement in median PFS (8.12 months; 95% CI, 4.51-11.12) compared with sacituzumab govitecan monotherapy (6.22 months; 95% CI, 3.85-8.68), although this improvement did not reach statistical significance (HR, 0.81; 95% CI, 0.51-1.28; P = .37). 

o   Immature OS data presented at the meeting highlighted a median OS of 18.52 months (95% CI, 16.55-not applicable [NA]) vs 17.96 months (95% CI, 12.50-NA) in each respective arm (HR, 0.65; 95% CI, 0.33-1.28; P = .21).







References





1.        Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). J Clin Oncol. 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000

2.        Kalinsky K, Bianchini G, Hamilton EP, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: primary outcome of the phase 3 postMONARCH trial. J Clin Oncol. 2024;42(suppl 17):LBA1001. doi:10.1200/JCO.2024.42.17_suppl.LBA1001

3.        Garrido-Castro A, Kim, SE, Desrosiers J, et al. SACI-IO HR+: a randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. J Clin Oncol. 2024;42(suppl 17):LBA1004. doi:10.1200/JCO.2024.42.17_suppl.LBA1004

In a conversation with CancerNetwork®, Jagoda Misniakiewicz, PharmD, a clinical pharmacy specialist in the Clinical Pharmacy and Outcomes Sciences Department at Hollings Cancer Center of the Medical University of South Carolina, spoke about the use of fruquintinib (Fruzaqla) as a treatment option for those with metastatic colorectal cancer (CRC).






The FDA previously approved fruquintinib as a treatment for those with metastatic CRC and prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and anti-VEGF therapy in November 2023.1





Misniakiewicz detailed the agent’s mechanism of action as a potent, orally available small molecule kinase inhibitor and its potential to inhibit blood vessel growth, thereby yielding vascular regression, normalization, and construction. Additionally, the clinical benefit of switching from intravenous therapy to this oral treatment appears to extend to any patient who has progressed on prior therapy, although she noted that there are currently no specific biomarkers or tumor characteristics that would make patients suitable candidates for fruquintinib.





The discussion also focused on the efficacy and safety data supporting the clinical utility of fruquintinib in this patient population. Specifically, Misniakiewicz highlighted the “exciting” progression-free survival (PFS) findings from the phase 3 FRESCO-2 trial (NCT04322539), which may affirm fruquintinib as a “promising treatment option” for those with refractory disease. 





According to previous findings from the FRESCO-2 trial published in Lancet Oncology, the median PFS was 3.7 months (95% CI, 3.5-3.8) with fruquintinib plus best supportive care vs 1.8 months (95% CI, 1.8-1.9) with placebo plus best supportive care (HR, 0.32; 95% CI, 0.27-0.39; P .0001).2 Additionally, the median overall survival (OS) was 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) in each respective arm (HR, 0.66; 95% CI, 0.55-0.80; P .0001). PFS and OS benefits across various patient subgroups—in which investigators stratified patients based on previous treatment with trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga), RAS mutation status, and duration of metastatic disease—were comparable with those observed in the intent-to-treat population.





“The truth is that treatment options for metastatic [CRC] are limited, and the approval of fruquintinib will hopefully bridge that gap a little bit,” Misniakiewicz said. “Oral agents have changed the landscape of treatment for patients with cancer. Furthermore, targeted agents allow us to tailor therapy with the goal of improving clinical outcomes while minimizing off target toxicities; fruquintinib will hopefully allow us to do this in patients with metastatic colorectal cancer.”






References





1.        Takeda receives U.S FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed June 6, 2024. https://bit.ly/3SwkD8U

2.        Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. Published online June 15, 2023. doi:10.1016/S0140-6736(23)00772-9

In a conversation with CancerNetwork®, Terence T. Sio, MD, MS, discussed how technological advancements in radiation oncology have impacted the modern treatment landscape for patients with non–small cell lung cancer (NSCLC).





Sio, a professor of radiation oncology at Mayo Clinic in Phoenix, Arizona, first outlined the use of immunotherapy and other systemic treatment options for this patient population. He detailed how the use of these modalities and other factors such as the risk of radiation-induced pneumonitis often inform the extent of subsequent radiotherapy. Treatment decision making may also involve collaboration with surgeons and medical oncologists as part of a multidisciplinary tumor board, which meets regularly at his institution to determine suitable strategies for those who require more than 1 course of therapy. 





Additionally, Sio spoke about currently prevalent radiotherapy treatment strategies for patients with NSCLC as well as possible toxicities that may be associated with these modalities. In terms of novel technology in the field, he highlighted the development of proton beam radiotherapy and the potential advantages it may offer over other therapies. 





According to Sio, use of proton beam radiotherapy may reduce excess radiation that usually extends beyond the targeted tumor, effectively lowering the risk of adverse effects (AEs) during treatment. Specifically, proton beam radiotherapy may benefit patient subgroups including those who have previously experienced a heart attack or those who are older and frailer. With an adequate treatment plan that encompasses the use of proton beam radiation, Sio stated that it may be possible to treat these subgroups with fewer AEs than those observed in patients who undergo standard radiotherapy. 





“We can actually be helping some of the patients who otherwise may not be able to stand as intensive of a method of combining radiation and chemotherapy for their lung cancer treatments,” Sio said regarding the use of proton beam radiotherapy in this population. “Right now, we have shown that proton [beam radiotherapy] has a role in lung cancer treatments.”

Through elaborate multidisciplinary collaboration, institutions with National Accreditation Program for Rectal Cancer (NAPRC) standards can deliver a “high level of care” in the surgical treatment of patients with rectal cancer, according to Steven Wexner, MD, PhD, and Arielle Kanters, MD.





In a conversation with CancerNetwork®, Wexner and Kanters detailed the history and advancement of the NAPRC as an interdisciplinary initiative to improve the outcomes of those undergoing surgery for rectal cancer.





Wexner is the chair in the Department of Colorectal Surgery and director of the Ellen Leifer Shulman & Steven Shulman Digestive Disease Center at Cleveland Clinic, Florida, the founding chair of the NAPRC for the American College of Surgeons Commission on Cancer, and part of the executive committee of the Commission on Cancer. Kanters is a colorectal surgeon, associate fellowship program director, and surgeon leader of the NAPRC program at Cleveland Clinic Main Campus.





Wexner spoke about the inspiration for developing the NAPRC as a mission to elevate the level of surgical outcomes in patients with rectal cancer across the United States to those he observed in European countries such as the United Kingdom and Scandinavia. He enlisted leaders from organizations including the Society of Surgical Oncology and the College of American Pathologists to outline and apply appropriate standards for surgical care in rectal cancer.





Additionally, Kanters highlighted how enforcing precise guidelines and compliance measures through the NAPRC program facilitates multidisciplinary efforts with colleagues who specialize in radiology and pathology. She stated that these principles help individuals develop their skills across each department, thereby maintaining a high level of treatment for patients with rectal cancer. 






Findings from a study published in the Journal of the American College of Surgeons indicated that mortality and complication rates appeared to be lower for patients who received surgery for rectal cancer at NAPRC-accredited institutions compared with those who were treated at non-accredited practices.





Wexner and Kanters also discussed how potential advancements related to the use of neoadjuvant or adjuvant therapy may further improve patient outcomes in the field. Additionally, they spoke about updated research on immunotherapy and other modalities that they anticipate at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.






Reference





Harbaugh CM, Kunnath NJ, Suwanabol PA, Dimick JB, Hendren SK, Ibrahim AM. Association of National Accreditation Program for Rectal Cancer Accreditation with outcomes after rectal cancer surgery. J Amer College Surg. Published March 28, 2024. doi:10.1097/XCS.0000000000001064

In a conversation with CancerNetwork® at Memorial Sloan Kettering Cancer Center (MSKCC), Neil M. Iyengar, MD, spoke about developments and challenges in his career as a medical oncologist and clinical investigator as well as ongoing research efforts in improving outcomes among patients with breast cancer. 





Iyengar, a breast oncologist in in the Department of Medicine at MSKCC and Weill Cornell Medicine in New York City, New York, as well as the co–editor-in-chief of the journal ONCOLOGY®, detailed his work in the emerging field of exercise oncology. Based on preclinical data supporting the potential anti-tumor effects of exercise, he and his colleagues are organizing several clinical trials to validate whether exercise intervention can improve cancer-specific end points. Although some findings may support implementing exercise as part of a cancer treatment plan, Iyengar noted the observational and self-reported nature of the prior data and said that it would be necessary to test exercise intervention in the same way “you would develop any new drug for treating cancer.”





Additionally, Iyengar discussed the fulfillment of ensuring patient care, a passion that has fueled his interest in lifestyle interventions such as exercise oncology. He highlighted how his cancer treatment philosophy extends beyond the goal of reducing tumor volumes to safeguarding the patient’s physical and emotional well-being.





“You can certainly hammer away at a tumor and give all kinds of chemotherapy and anti-cancer therapies, but if that [patient] is feeling miserable and has no quality of life and a short duration of response to that therapy, that’s not necessarily the type of outcome that I would consider to be successful,” Iyengar said. “If you’re able to either control or cure a cancer while also improving a [patient’s] quality of life and general well-being, that’s the kind of outcome that I strive for. When I see that in my patients and in the patients of my colleagues, that certainly brings a lot of fulfillment.”





Iyengar also highlighted how he found excitement and passion in off-hours responsibilities to help achieve work-life balance. Looking ahead, he spoke about data on anti-estrogen agents, antibody drug conjugates, and other breast cancer treatment strategies that he is looking forward to hearing at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.