AACR 2026: Real-World Data Show Targeted Therapy Extends Survival in Aggressive Form of Colorectal Cancer

BUFFALO, N.Y. and SAN DIEGO — HER2-positive, metastatic colorectal cancer is an aggressive disease that often shows limited response to standard chemotherapy. A new study from Roswell Park Comprehensive Cancer Center, highlighted today at the 2026 annual meeting of the American Association for Cancer Research (AACR) in San Diego, California, suggests that patients with HER2‑positive metastatic colorectal cancer may live longer when treated with the targeted therapy trastuzumab deruxtecan (T‑DXd, brand name Enhertu) compared to standard chemotherapy. The findings provide important evidence that the survival benefits previously seen in clinical trials also hold up in everyday cancer care.

While clinical trials have demonstrated that trastuzumab deruxtecan (T-DXd/Enhertu) can prolong overall survival, until now its effectiveness outside the context of a clinical trial has been unclear. Zunairah Shah, MBBS, co-first author of the study, will share her team’s findings in Abstract 1303, “Real-world overall survival with trastuzumab deruxtecan versus standard chemotherapy in HER2-amplified MSS metastatic colorectal cancer,” Sunday, April 19, 3:35-3:50 p.m. PDT in room 17, Mezzanine Level of the San Diego Convention Center. 

T-DXd, a type of targeted therapy called an antibody-drug conjugate, delivers chemotherapy directly to cancer cells that overexpress the protein HER2, bypassing healthy cells. Past clinical trials evaluated T-DXd in patients who had received two or more prior lines of therapy. However, in other tumor types, antibody-drug conjugates have shown greater benefit when used earlier in the treatment course, as seen in DESTINY-Breast09. Consequently, the team retrospectively compared outcomes in patients who received T-DXd in the second-line setting versus standard chemotherapy.

“Our study suggests that T-DXd may improve long-term survival when used earlier in treatment, with manageable real-world safety,” explains Dr. Shah, Hematology/Oncology Fellow at Roswell Park.

To provide a more accurate assessment of the drug’s effects outside of a clinical trial, Dr. Shah and her colleagues analyzed data from 11,112 patients, including 9,135 treated with standard chemotherapy and 1,977 treated with T-DXd. While overall survival was similar at one year, at five years T-DXd showed a clear advantage, with a 58% overall survival rate compared with 49% in the standard chemotherapy group.

“In this study, trastuzumab deruxtecan was associated with improved long-term survival compared with standard chemotherapy, along with a lower risk of death and a manageable safety profile,” says Dr. Shah. “These findings suggest it may offer a meaningful benefit for patients with HER2-positive metastatic colorectal cancer, improving outcomes in this aggressive disease.”

“While trastuzumab deruxtecan has typically been used in advanced colorectal cancer in later lines of therapy — third line or beyond — this retrospective real-world study shows that patients had improved survival outcomes if T-DXd was used earlier in patients with HER2-positive colorectal cancer. “However, prospective clinical trials are needed to validate these findings. Pulmonary toxicity will also need to be considered in patients who receive T-DXd,” adds Kannan Thanikachalam, MD, Assistant Professor of Gastrointestinal Medical Oncology, Department of Medicine, co-senior author of the study. 

“Results from this study are strikingly similar to trial data from HER2-positive metastatic breast cancer showing preserved or improved efficacy of trastuzumab deruxtecan when used in earlier lines,” says Sheheryar Kabraji, BMBCh, Chief of Breast Medicine and Director of Breast Translational Research at Roswell Park, also co‑senior author of the study. “This work is an important example of how clinicians can use real-world data to optimize therapies for an aggressive cancer like HER2-positive colorectal disease. Analyses like this help move the field toward more precise, evidence‑based treatment strategies that can ultimately improve patient outcomes.”

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From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. The Roswell Park team of 4,000+ makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Rated “Exceptional” by the National Cancer Institute, Roswell Park, founded in 1898, was one of the first NCI-designated comprehensive cancer centers in the country and remains the only one in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email ASKRoswell@RoswellPark.org.