This year’s ASCO meeting unites nearly 45,000 oncology professionals to discuss leading-edge scientific data and attend educational sessions, empowering health care teams to deliver more personalized and effective lifesaving cancer care to patients.
Highlights of City of Hope’s ASCO data include the below, which focus on breast, genitourinary and gastrointestinal cancers.
1015: Real-world data show it is safe to readminister trastuzumab-deruxtecan to metastatic breast cancer patients who experience low-grade lung complications
Attend: Friday, May 30 at 2:57 p.m. CDT in Hall D2
A large, multicenter retrospective study further supports the safety of readministering the antibody-drug conjugate trastuzumab-deruxtecan (T-DXd) to metastatic breast cancer patients after initial drug pauses due to low-grade interstitial lung disease (ILD), which is defined as radiographic evidence of lung inflammation without associated symptoms.
T-DXd is approved for HER2+ and HER2-low and ultra-low advanced breast cancer as well as for many other solid tumors. It carries a rare but serious risk of ILD, requiring frequent imaging and symptom evaluation. Guidelines recommend permanent discontinuation for grade 2 (symptomatic) or higher ILD, but physicians can choose to readminister T-DXd to patients with asymptomatic grade 1 ILD after resolution of imaging findings.
This real-world data of 712 metastatic breast cancer patients treated with T-DXd is significant because limited data exists on the outcomes of readministering T-DXd or “rechallenge” after ILD. The only other dataset included a pooled analysis of nine clinical trials and was presented by Hope S. Rugo, M.D., F.A.S.C.O., City of Hope Women’s Cancers Program director; professor, Department of Medical Oncology & Therapeutics Research, at the 2024 ESMO Breast Cancer Annual Congress. This pooled data was recently submitted for publication.
“The real-world data shows that patients with metastatic breast cancer who were treated with trastuzumab-deruxtecan experienced prolonged clinical benefit even if it had to be discontinued temporarily due to low-grade interstitial lung disease. Importantly, patients treated with steroids had faster radiographic ILD improvement, highlighting the importance of early steroid use,” said, Dr. Rugo, corresponding author of the ASCO abstract.
The researchers collected patient demographics, T-DXd and steroid dosing, imaging results, and outcomes after rechallenge. About 9% of the study’s patients experienced ILD at some level. Some 47 patients were rechallenged — 81% after grade 1 ILD. Among the patients with grade 1 ILD, 56% received steroids for a median of 36 days. Radiographic improvement was seen at a median of 24 days for patients treated with steroids vs. 82 days for those who did not receive steroids.
Among patients rechallenged after grade 1 ILD, recurrent ILD rates were low, with the majority being grade 1. None were grade 5. After rechallenge, patients remained on T-DXd for a median of 215 days. About 26% developed recurrent ILD at a median of 211 days from rechallenge.
4510: Tracking the genomic evolution of kidney cancer and recurrence to identify biomarkers of care
Attend: Saturday, May 31 at 4:54 p.m. CDT in the Arie Crown Theater
Some 20% of renal cell carcinoma (RCC) patients who undergo curative kidney cancer surgery experience disease recurrence. Experts have evaluated in a Phase 3 trial (IMmotion010) whether administering monoclonal antibody atezolizumab post-surgery could prevent RCC from returning and found that it did not.
However, a precision medicine study led by City of Hope’s Sumanta Kumar Pal, M.D., F.A.S.C.O., found that patients who had specific genomic biomarkers in that Phase 3 trial experienced longer disease-free survival when atezolizumab was used after kidney resection.
“We continue to investigate the genetics of kidney cancer patients to understand how we can use this information to prolong life. This study builds on a biomarker, KIM-1, that can identify RCC patients who benefit from adjuvant atezolizumab by using tumor-based genomic features,” said Dr. Pal, City of Hope professor, Department of Medical Oncology & Therapeutics.
In the study, the researchers obtained pretreatment tumor tissue samples from 754 patients. Qualifying patient samples were categorized into seven molecular subgroups and further split as biomarker KIM-1 high or KIM-1 low. The scientists found that patients in cluster 6 (stromal/proliferative) appeared to benefit from atezolizumab (n=50). Additionally, patients with KIM-1-high biomarkers and more Teff cells responsible for facilitating immune responses were linked to longer disease-free survival when adjuvant atezolizumab was administered.
“KIM-1 is the most robust predictor of outcome with atezolizumab. We performed whole transcriptome sequencing of RCC tumors before using atezolizumab as well as at disease recurrence, when able, and spotlighted a genomic evolution in disease progression that offers insights into why patients with RCC relapse. Further defining these biomarkers will allow oncologists to provide more personalized care to kidney cancer patients,” said Dr. Pal, who is a paid consultant to Roche, the manufacturer of atezolizumab.
3553: A combination treatment of checkpoint inhibitors Vilastobart and atezolizumab shows promise in patients with advanced colorectal cancer
Visit: Saturday, May 31, from 9 a.m. to noon CDT in Hall A
In Phase 2 of a safety and tolerability clinical trial, metastatic colorectal cancer patients who have microsatellite stability (MSS) demonstrated initial evidence of anti-tumor activity when treated with the checkpoint inhibitors Vilastobart (XTX101) and atezolizumab. About 96% of metastatic colorectal cancer cases are MSS.
“This finding is noteworthy because we are seeing a novel combination therapy shrink tumors in a patient population with advanced solid tumors that historically have been nonresponsive to immune checkpoint inhibitors,” said Marwan Fakih, M.D., City of Hope professor, Department of Medical Oncology & Therapeutics Research, and lead author of the abstract.
As of this January, 40 patients with MSS colorectal cancer were dosed in Phase 2 of the trial. About 70% of patients had had three or more prior lines of therapy. Those who were previously treated with a type of immune checkpoint inhibitor were excluded.
On the Phase 2 trial, 27% of patients without liver metastatic disease experienced a partial response, defined as more than 50% shrinkage of target lesions. Patients with tumor shrinkage had a significant decrease in circulating tumor DNA, further confirming the clinical efficacy of this combination. The combination was safe as it was associated with a low rate of severe immune-related complications. The safety was further demonstrated by a very low rate of treatment discontinuation.
Vilastobart is an investigational checkpoint inhibitor being developed by Xilio Therapeutics, a company licensing City of Hope technology and co-founded by City of Hope’s Dr. John Williams. Dr. Fakih is a paid advisory board member of Xilio Therapeutics.
5041: Using real-world data to provide insights into treatment that has a lower chance of causing heart attack and stroke in prostate cancer patients
Visit: Monday, June 2, from 9 a.m. to noon CDT in Hall A
A study led by City of Hope’s Alan H. Bryce, M.D., provides decision-making insights to aid with the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), especially those at high risk of cardiovascular events like heart failure and stroke.
The study used real-world data to confirm clinical trial findings which suggest mCRPC patients who have never had chemotherapy and were treated with testosterone blocker abiraterone acetate have a higher risk of hospitalization due to cardiovascular events than patients treated with androgen receptor inhibitor enzalutamide.
Dr. Bryce led a group of scientists who analyzed the data of more than 68 million seniors who are U.S. Medicare and Medicaid beneficiaries. They included mCRPC patients who were 65 or older and have never had chemotherapy. Patients were then stratified into subgroups based on cardiovascular disease history.
People treated with abiraterone acetate had a statistically significant higher risk of experiencing cardiovascular events like heart attacks, strokes, coronary revascularization to restore blood flow, heart failure, irregular heart rhythm and blood clots compared to mCRPC patients treated with enzalutamide. Additionally, the researchers found that the risk of death was higher with abiraterone acetate than with enzalutamide regardless of cardiovascular disease history.
“Real-world data studies like this one are crucial because they provide a broader, more representative perspective on health and disease compared to data from clinical trials, which usually are conducted in controlled settings. Large data sets allow for deeper understanding of how treatments affect patients in real-life scenarios and includes factors not captured in carefully designed clinical trials,” said Dr. Bryce, who is a paid speaker for Pfizer, the manufacturer of enzalutamide.
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About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked Top 5 “Best Hospital” in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
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