Kristen K. Ciombor, MD, MSCI, assistant professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the use of panitumumab (Vectibix) in the maintenance treatment of patients with 

 wild-type metastatic colorectal cancer (mCRC).

The phase 2 PANAMA trial (AIO KRK 0212 trial; NCT01991873), data of which were originally 

presented during the 2021 ASCO Annual Meeting

, investigated the addition of panitumumab to 5-fluorouracil (5-FU) and leucovorin as maintenance treatment in this population. The patients enrolled to the trial received up-front FOLFOX (5-FU and oxaliplatin) plus panitumumab. Those who achieved disease control, defined as complete remission or stable disease, were then randomized 1:1 to receive panitumumab plus 5-FU/leucovorin or 5-FU/leucovorin alone.

Optimal maintenance therapy following treatment with fluoropyrimidine, oxaliplatin, and EGFR-based induction therapy remains unclear. The trial deepened the understanding of options available to patients who receive up-front anti-EGFR therapy, Ciombor says. However, panitumumab may not always be the optimal option for patients with mCRC in the maintenance setting due to its toxicities, Ciombor concludes.

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Kristen K. Ciombor, MD, MSCI, discusses the use of panitumumab in the maintenance treatment of patients with RAS wild-type metastatic colorectal cancer.

Dr. Ciombor on the Utilization of Maintenance Panitumumab in RAS Wild-Type Metastatic CRC

Kristen K. Ciombor, MD, MSCI, assistant professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the use of anti-EGFR therapy for the frontline treatment of patients with metastatic colorectal cancer (CRC).

Multiple studies have examined how to incorporate these agents into the first-line setting for patients with RAS-mutant or wild-type disease, according to Ciombor. The phase 3 CALGB/SWOG 80405 trial (NCT00265850) examined cetuximab (Erbitux) and/or bevacizumab (Avastin) in combination with chemotherapy in patients with metastatic CRC, and the phase 2 DEEPER study (NCT02515734) evaluated the combination FOLFOXIRI plus cetuximab vs FOLFOXIRI and bevacizumab in those with RAS wild-type disease.

The primary end point of DEEPER was depth of response, Ciombor notes. Results showed that patients in the cetuximab arm of the trial experienced deeper responses than those in the bevacizumab arm; however, it is still unknown how this information translates to overall survival and other important end points, Ciombor concludes.

Kristen K. Ciombor, MD, MSCI, discusses the use of anti-EGFR therapy for the frontline treatment of patients with metastatic colorectal cancer.

Dr. Ciombor on Anti-EGFR Therapy in Metastatic CRC

Kristen K. Ciombor, MD, MSCI, an assistant professor of medicine in the Division of Hematology/Oncology, Department of Medicine at Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses responses achieved with preoperative chemoradiation in patients with rectal cancer.

Patients who enrolled on the phase 3 RAPIDO trial (NCT01558921) were randomized to the experimental arm of short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME), or the control arm of chemoradiation, TME, and adjuvant chemotherapy, Ciombor says. Nearly all patients in the study had a high chance of undergoing surgery and having an R0 resection, but the rate of pathologic complete response nearly doubled for patients in the experimental arm, Ciombor notes.

The primary end point of the study was disease-related treatment failure; this was statistically significantly better in the experimental arm, Ciombor explains. Additionally, distant metastases were less commonly observed in the experimental arm. More mature data are needed regarding locoregional progression, but at 3 years, no statistically significant difference was observed between the 2 arms. However, a slight trend toward increased rates of locoregional progression was noted in the experimental arm, Ciombor says. 

The overall survival rates in the experimental and control arms were 89.1% and 88.9%, respectively, at 3 years despite the high-risk patient population, Ciobmor concludes.

Kristen K. Ciombor, MD, MSCI, discusses responses achieved with preoperative chemoradiation in patients with rectal cancer.









Dr. Ciombor on the Efficacy of Preoperative Chemoradiation in Rectal Cancer

Kristen K. Ciombor, MD, MSCI, an assistant professor of medicine in the Division of Hematology/Oncology, Department of Medicine at Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses ongoing research efforts being made in rectal cancer.

Many treatment options are available for patients with locally advanced rectal cancer, however, there is still a need for further studies to be conducted in this patient population, including efforts focused on biomarker selection, Ciombor says. Novel efforts may lead to the development of non-operative strategies in patients who would otherwise have their rectum surgically resected or provide further opportunities to improve outcomes through personalized approaches, Ciombor adds.

For example, an ongoing study being conducted by the Eastern Cooperative Oncology Group will examine the use of immunotherapy versus chemotherapy or chemoradiation in patients with microsatellite instability–high disease. Based on the efficacy immunotherapy has demonstrated in patients with metastatic disease, investigators will examine the use of nivolumab (Opdivo) and ipilimumab (Yervoy) plus short-course radiation therapy, Ciombor concludes.

Kristen K. Ciombor, MD, MSCI, discusses ongoing research efforts being made in rectal cancer.

Dr. Ciombor on Ongoing Research Efforts in Rectal Cancer

Kristen K. Ciombor, MD, MSCI, an assistant professor of medicine in the Division of Hematology/Oncology, Department of Medicine at Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses sequencing treatment options for patients with locally advanced rectal cancer.

The process of sequencing therapies in this patient population has undergone various changes in recent years, according to Ciombor. Previously, patients with locally advanced disease would receive chemoradiation followed by total mesorectal excision followed by adjuvant chemotherapy, says Ciombor.

In light of new data from multiple clinical trials, several approaches can be used for these patients, Ciombor adds. Sequencing decisions can be difficult, as this must be tailored to each individual patient. Recent findings from several studies presented during the 

 have helped to clarify which therapies are best suited to each patient, Ciombor says. 

The total neoadjuvant approach is commonly used at Vanderbilt University Medical Center, according to Ciombor. Chemotherapy is being used either as a first-line treatment or preoperatively in that setting. Many patients with locally advanced rectal cancer tend to have bulky disease with either T4 lesions or many nodes, which could put them at risk for distant metastases, adds Ciombor. For those patients, it's important to start with chemotherapy as a frontline treatment, Ciombor explains. Surgery still has a place in the treatment paradigm, but chemotherapy and chemoradiation are best used in the up-front setting, Ciombor concludes.

Kristen K. Ciombor, MD, MSCI, discusses sequencing treatment options for patients with locally advanced rectal cancer.

Dr. Ciombor on Sequencing Therapies in Locally Advanced Rectal Cancer

Kristen K. Ciombor, MD, MSCI, assistant professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive metastatic gastric cancer. 

 for the treatment of patients with locally advanced or metastatic HER2-positive gastric/gastroesophageal junction (GEJ) cancer who received a prior trastuzumab (Herceptin)-based regimen. The regulatory decision was based on findings from the phase 2 DESTINY-Gastric01 trial in which the antibody-drug conjugate improved overall survival and induced a higher objective response rate compared with chemotherapy in this patient population. 

Trastuzumab deruxtecan is a welcome addition to the gastric/GEJ cancer armamentarium, says Ciombor. However, as some patients will lose HER2 expression, routine biopsies are needed to determine whether the patient expresses the HER2 target and is still eligible to receive trastuzumab deruxtecan, Ciombor concludes. 

Kristen K. Ciombor, MD, MSCI, discusses the FDA approval of fam-trastuzumab deruxtecan-nxki in HER2-positive metastatic gastric cancer.  



Dr. Ciombor on the FDA Approval of Trastuzumab Deruxtecan in HER2+ Metastatic Gastric Cancer 

Kristen Ciombor, MD, MSCI, assistant professor of medicine, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the goals of the COLOMATE protocol in metastatic colorectal cancer (mCRC).

COLOMATE is an umbrella screening protocol that is seeking to match patients in academic and community centers with appropriate targeted therapy, explains Ciombor. Patients will undergo molecular profiling or liquid biopsy, and according to their profile, will be directed to an appropriate basket trial through the ACCRU network.

Currently-accruing trials include those evaluating anti-HER2, EGFR rechallenge, and anti-FGFR strategies, among others. An additional basket trial will evaluate therapies for patients without activating alterations in an attempt to identify treatments for those who have exhausted standard therapy, says Ciombor.

In addition to identifying potentially beneficial treatments, liquid biopsies can be used to monitor a patient's response to treatment over time. These tests can also detect, through circulating tumor DNA, whether the patient is responding to treatment earlier than CT scans or other imaging modalities. In the absence of response, liquid biopsies may also be able to identify mechanisms of resistance and inform additional targeted strategies, concludes Ciombor.

Dr. Ciombor on the Goals of the COLOMATE Trial in mCRC

Kristen Ciombor, MD, MSCI, assistant professor of medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the role of liquid biopsies in colorectal cancer (CRC).

Over the last decade or so, the gold standard has been tissue-based molecular profiling, Ciombor says. Technology has since advanced, enabling patients to undergo liquid biopsies as a way of identifying alterations and monitoring their tumor for patterns of resistance. The field is moving very quickly in this space. At this pace, patients may not have to undergo invasive tissue biopsies. Ideally, the goal of liquid biopsies is to provide a more precision-based approach to patients in detecting mechanisms of resistance to therapy.

In CRC, a number of biomarkers have emerged that can be paired with effective targeted therapy. For example, patients who express microsatellite instability—high or mismatch repair deficiency in their tumors can benefit from checkpoint inhibitors. There are also FDA-approved therapies for patients with 

 fusions and promising targeted agents for patients who harbor 

 mutations. Recent data have shown that liquid biopsies can detect these molecular characteristics with high sensitivity.

Kristen Ciombor, MD, MSCI, assistant professor of medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, discusses the role of liquid biopsies in colorectal cancer.

Kristen Ciombor, MD, MSCI

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