Dr Eng on Unmet Needs Within the mCRC Treatment Paradigm

Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology, professor, medicine, Hematology and Oncology, director, Strategic Relations, co-director, Gastrointestinal (GI) Oncology, co-leader, GI Cancer Research Program, director, Young Adult Cancers Program, Vanderbilt-Ingram Cancer Center, discusses unmet needs within the metastatic colorectal cancer (mCRC) treatment paradigm.

One significant unmet need in the management of mCRC is addressing 

 V600E–mutant tumor types, particularly in microsatellite-stable (MSS) patients, Eng begins. Although the 

 for the treatment of previously treated adult patients with 

V600E–mutated mCRC, there is still a lack of effective options once patients progress after BRAF inhibitor therapy, she says. The ongoing phase 3 BREAKWATER trial (NCT04607421), which is evaluating the combination of encorafenib and chemotherapy in the frontline 

 V600E–mutated mCRC setting, holds promise, but final results are still pending, Eng reports. This leaves clinicians unsure of how best to treat patients who progress on BRAF-targeted therapies, according to Eng. In these cases, it is critical to consider clinical trials for all patients, regardless of mutation status or current treatment, she adds.

Another major area of interest is addressing 

 mutations, particularly since the combination of 

 G12C–mutated mCRC, Eng expands. There is also research into targeting 

 G12V mutations with combination therapies, but patients with other 

 mutations still lack viable treatment options, she notes. Eng adds that this unmet need has led to significant interest in the development of pan-RAS inhibitors, although these treatments are still in the early stages of research.

The refractory patient population remains another area of unmet need, especially for those without actionable mutations, Eng continues. Although therapies targeting HER2-amplified mCRC have shown some success, many patients still lack effective treatment options, she reports. Ongoing research offers hope, but for now, participation in clinical trials is essential for patients with surgically unresectable disease, Eng emphasizes. Clinical trials provide access to emerging therapies and help address the gaps in available treatments for this challenging-to-treat patient population, she concludes.

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Cathy Eng, MD, FACP, FASCO, discusses unmet needs within the metastatic colorectal cancer treatment paradigm.

End of Year Review in CRC: Exploring Emerging Treatment Options and Clinical Insights on the Future Landscape

Cathy Eng, M, FACP, FASCO, presents a comprehensive End-of-Year Review in Colorectal Cancer (CRC), delving into the exploration of emerging treatment options and clinical insights on the future landscape. This insightful review includes a focus on the recent approval of fruquintinib and important updates on target therapies for HER2+, BRAF V600E-Mutant, and KRAS-mutant CRC, as well as an interactive Q&A segment.

Cathy Eng, MD, FACP, FASCO, the David H. Johnson Chair in Surgical and Medical Oncology, co-leader, Gastrointestinal (GI) Cancer Research Program, professor, medicine, Hematology and Oncology, co-director, GI Oncology, Vanderbilt-Ingram Cancer Center; vice-chair, SWOG GI Committee; director, Vanderbilt-Ingram Cancer Center Young Adult Cancers Initiative, discusses the ongoing investigation of fruquintinib (HMPL-013) in patients with relapsed/refractory metastatic colorectal cancer (mCRC).

At the 2023 ASCO Annual Meeting, investigators presented updated data

 on the use of fruquintinib in patient with mCRC from subgroup analyses of the phase 3 FRESCO-2 trial (NCT04322539). Data from this analysis showed that treatment with fruquintinib and best supportive care (BSC) elicited improvements in overall survival (OS) and progression-free survival vs placebo plus BSC in this patient population, irrespective of the number of prior lines of therapy or types of prior treatment patients had received. Among all 461 patients treated with fruquintinib, the median OS was 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) with placebo (n = 230; HR, 0.662; 95% CI, 0.549-0.800; 

in May 2023, the FDA granted priority review to a new drug application

 seeking the approval of fruquintinib forthe treatment of patients with previously treated mCRC.

Eng states that this is a current area of anticipation as investigators await final data from the FRESCO-2 trial. She explains that she and other investigators are eagerly awaiting the potential FDA approval of fruquintinib in the relapsed/refractory mCRC patient cohort. This treatmentconsists of a selective oral TKI designed to target VEGF receptors 1, 2, and 3, Eng explains. The data obtained from the trial show an improved OS with fruquintinib, particularly in patients who had received an average of 4 prior lines of therapy, she emphasizes.

Notably, in FRESCO-2, treatment with fruquintinib wasn't limited by number of prior lines of therapy. Given the oral formulation of fruquintinib, investigators are hopeful for its approval, Eng concludes.

Cathy Eng, MD, FACP, FASCO, discusses the ongoing investigation of fruquintinib in patients with relapsed/refractory metastatic colorectal cancer.


Dr Eng on the Ongoing Investigation of Fruquintinib in Relapsed/Refractory mCRC

Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair, Surgical and Medical Oncology, co-leader, Gastrointestinal (GI) Cancer Research Program, professor of medicine, hematology and oncology, co-director, GI Oncology, vice chair, SWOG GI Committee, and director, VICC Young Adult Cancers Initiative, Vanderbilt-Ingram Cancer Center, discusses the rising incidence of early-onset colorectal cancer (CRC).

Although the median age of onset for CRC in the United States is around 67 years, the incidence of early-onset CRC is rising among young patients, says Eng. In large referral centers, oftentimes patients are innately younger because they are getting second opinions from primary care facilities, says Eng. However, an increased number of very young patients with sporadic CRC has been observed in recent years, Eng explains.

 by lead author Christina E. Bailey MD, MSCI, of Vanderbilt-Ingram Cancer Center demonstrated a significant increase in the incidence of young adults diagnosed with CRC and a decline in diagnoses in older patients. These findings have since been validated in other clinical studies, says Eng. Moreover, research suggests that a significant increase in the incidence of left-sided CRC will be seen in the coming years, concludes Eng. 

Cathy Eng, MD, FACP, FASCO, discusses the rising incidence of early-onset colorectal cancer.  



Dr. Eng on the Rising Incidence of Early-Onset CRC 

Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal (GI) Cancer Research Program, professor of medicine in hematology and oncology, co-director of GI Oncology, vice chair of the SWOG GI Committee, and director of the VICC Young Adult Cancers Initiative at Vanderbilt-Ingram Cancer Center, discusses the ongoing phase 3 FRESCO-2 trial (NCT04322539) in metastatic colorectal cancer (mCRC). 

The global, double-blind, placebo-controlled FRESCO-2 trial is randomizing patients with mCRC 2:1 to fruquintinib plus best supportive care vs placebo plus best supportive care. Eligible patients had to have received prior regorafenib (Stivarga) and/or trifluridine/tipiracil (TAS-102; Lonsurf). The primary end point of the study is overall survival, Eng explains. 

Fruquintinib is a potent, highly selective, oral VEGF1/2/3 TKI that is approved in China to treat patients with mCRC who have been previously treated with fluoropyrimidine, oxaliplatin, and irinotecan. In the United States, the FDA granted a fast track designation to fruquintinib for the treatment of patients with mCRC who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, VEGF-directed therapy, and if 

Cathy Eng, MD, FACP, FASCO, discusses the ongoing phase 3 FRESCO-2 trial in metastatic colorectal cancer.  



Dr. Eng Discusses the Ongoing FRESCO-2 Trial in mCRC

Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair in Surgical and Medical Oncology, co-leader, Gastrointestinal (GI) Cancer Research Program, professor of medicine (hematology and oncology), co-director, GI Oncology, vice chair, SWOG GI Committee, and director, VICC Young Adult Cancers Initiative, Vanderbilt-Ingram Cancer Center, discusses the features of high-risk colorectal cancer (CRC). 

Patients with CRC who are at a high risk of disease recurrence may have an obstruction or perforation at presentation, Eng says.

Additionally, patients who derive a suboptimal response to lymph node dissection, have positive margins, or have evidence of lymphovascular or pleural invasive disease are considered to be high-risk patients, explains Eng. 

Finally, patients with poorly differentiated or signet ring cell histologies are at an innately higher risk of disease recurrence compared with patients with other histologic CRC subtypes, concludes Eng.

Cathy Eng, MD, FACP, FASCO, discusses the features of high-risk colorectal cancer.  


Dr. Eng on Features of High-Risk CRC 

Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair in Surgical and Medical Oncology, co-leader, Gastrointestinal (GI) Cancer Research Program, professor of medicine (hematology and oncology), co-director, GI Oncology, vice chair, SWOG GI Committee, and director, VICC Young Adult Cancers Initiative, Vanderbilt-Ingram Cancer Center, discusses the role of adjuvant chemotherapy in colorectal cancer (CRC). 

Adjuvant chemotherapy provides patients with a reduced risk of disease recurrence, Eng explains.

Historically, adjuvant chemotherapy was given to patients with stage III, lymph node–positive disease following colon resection, explains Eng. Patients with stage II disease may also be eligible to receive adjuvant chemotherapy. Ultimately, that decision should be based on a discussion with the patient. 

Primarily, patients with colon cancer are candidates for adjuvant chemotherapy vs those with rectal carcinoma, Eng says.

Ongoing research efforts within the rectal carcinoma paradigm are evaluating moving available treatment options to the neoadjuvant setting, concludes Eng. 

Cathy Eng, MD, FACP, FASCO, discusses the role of adjuvant chemotherapy in colorectal cancer.  



Dr. Eng on the Role of Adjuvant Chemotherapy in CRC 

Cathy Eng, MD, FACP, FASCO, professor of hematology/oncology, co-leader, Gastrointestinal Cancer Research Program, Vanderbilt-Ingram Cancer Center, discusses the need to increase awareness regarding treating adolescents and young adults with colorectal cancer (CRC).

There is increased awareness regarding younger patients with CRC, though there is still a large unmet need with how to prepare this patient population for treatment, including preparing for psychosocial issues, financial hardship, job security concerns, and fertility preservation, explains Eng.

Typically, oncologists are treating elderly patients with CRC. Adolescents and young adults with CRC in hospitals are having treatment tailored toward the pediatric patient population, says Eng. Adolescents and young adults fall into a middle category and do not where to go, but hopefully awareness of this patient population will continue to increase, concludes Eng.

Cathy Eng, MD, FACP, FASCO, discusses the need to increase awareness regarding treating adolescents and young adults with colorectal cancer.

Dr. Eng on Increasing Awareness for Adolescents/Young Adults With CRC

Cathy Eng, MD, FACP, FASCO, professor of hematology/oncology, co-leader, Gastrointestinal Cancer Research Program, Vanderbilt-Ingram Cancer Center, discusses ways to address unmet needs for young adults with colorectal cancer (CRC).

Eng suggests opening up the communication to see what patients with CRC need. Young patients with CRC tend to see other doctors for second opinions and some cancer centers are opening clinics tailored to this young patient population. At Vanderbilt-Ingram Cancer Center, Eng is opening one such young adult cancer center in her new position.

Originally, this cancer center for young adults was going to be focused on gastrointestinal cancers, but Eng soon realized there were other oncologists who were looking for the same resources for their patients as her. Now, Eng is working with colleagues from different oncology sections to create a center of resources for young adults with cancer, including fertility preservation, nutrition, social work, fitness, and more.

Cathy Eng, MD, FACP, FASCO, discusses ways to address unmet needs for young adults with colorectal cancer.

Dr. Eng on Addressing Unmet Needs for Colorectal Cancer

Cathy Eng, MD, FACP, FASCO, professor of hematology/oncology, co-leader, Gastrointestinal Cancer Research Program, Vanderbilt-Ingram Cancer Center, discusses unique barriers facing patients with early-onset colorectal cancer (CRC).

There is expected to be a rise in the incidence of colon cancer and rectal carcinoma in patients in their 20s and 30s, says Eng. The average age of patients with CRC is 67 years old.

Patients with early-onset disease may face specific challenges such as psychosocial issues, financial hardship, job security concerns, and fertility preservation, says Eng.

Increasing awareness of these challenges and providing patients with optimal referrals to address these challenges are crucial, concludes Eng.  

Cathy Eng, MD, FACP, FASCO, discusses unique barriers facing patients with early-onset colorectal cancer. 
 

Cathy Eng, MD, FACP, FASCO

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