Rocío García-Carbonero, MD
The prospective, observational, real-world PROMETCO study (NCT03935763) may help address the evidence gap in third-line treatment of patients with metastatic colorectal cancer (mCRC), particularly among those with poorer performance statuses who are often underrepresented in clinical trials, according to Rocío García-Carbonero, MD.
In the second part of an interview with OncLive®, García-Carbonero discussed findings presented at the 2025 ESMO Gastrointestinal Cancers Congress showing an increase in adverse effects (AEs) and serious AEs among patients with mCRC being treated in the third-line setting who had an ECOG performance status of 2.
In a separate session on gastrointestinal neuroendocrine tumors (GI NETs), García-Carbonero highlighted the importance of molecular profiling in managing poorly differentiated neuroendocrine carcinoma of the colon—a highly aggressive subtype with poor prognosis—and underscored the need for education on diagnostic nuances.
In the first part of the interview, García-Carbonero detailed findings from a subgroup analysis of the phase 3 FRESCO-2 trial (NCT04322539) evaluating fruquintinib (Fruzaqla) in mCRC, exploring outcomes based on metastatic sites.
OncLive: What was the rationale for initiating the PROMETCO study, and why was it important to capture real-world outcomes specifically in patients receiving third-line therapy for mCRC?
García-Carbonero: The PROMETCO study is a real-world, prospective study. I believe it’s the first international, real-world, prospective study conducted in patients with mCRC who have progressed on 2 prior lines of therapy since their diagnosis of metastatic disease and were about to start a third-line treatment. That’s when patients consented to enrollment.
We collected prospective data from real-world clinical practice, including treatment patterns, safety, efficacy, progression-free survival [PFS], and overall survival. It’s an important study—it enrolled 738 patients and reflected the current real-world standard of care.
Importantly, the study included approximately 10% of patients with an ECOG performance status of 2, a subgroup that is generally underrepresented in clinical trials. It’s critical that we gather efficacy and safety data in this population.
What findings were observed, particularly regarding safety and outcomes in patients with poorer performance status?
We presented a safety analysis based on performance status. We also examined baseline characteristics in the subgroup of patients with poorer performance status. We found that patients with ECOG performance status of 2 tended to have more advanced disease, a higher incidence of right-sided colon cancer, greater liver involvement, and a higher number of metastatic sites overall.
These disease characteristics translated to approximately a 10% higher rate of AEs and serious AEs in this subgroup, with the most notable increase observed in anemia—likely reflecting the burden of more advanced disease.
These findings are important for practicing clinicians, [as they] provide insight into what to expect when treating patients who are frequently underrepresented in clinical trials.
Moving on to your session on outcomes in patients with GI NETs, what were your key takeaways for clinicians regarding the prognosis of patients in real-world clinical practice?
The session on GI NETs was very pragmatically oriented. The 3 case [studies] we discussed represented the spectrum of neuroendocrine neoplasms we encounter in clinical practice. This is a highly heterogeneous group of tumors, [ranging from] very indolent disease to [highly aggressive forms]. Patients often assume that all NETs or neoplasms are indolent, but that’s not always the case.
What were the key diagnostic and molecular insights from the poorly differentiated GI neuroendocrine carcinoma case that are important for clinicians to consider?
I presented a case of poorly differentiated neuroendocrine carcinoma of the colon, which is a scenario with a very poor prognosis and represents a highly aggressive tumor type. We discussed diagnostic procedures that may be indicated [in such cases]. For example, during this interactive session, we posed questions to the audience. It was striking to see that 25% of respondents said they would order a gallium PET scan. However, gallium PET imaging is indicated for well-differentiated tumors because it assesses somatostatin receptor expression, and it’s not appropriate for poorly differentiated carcinomas.
Another key takeaway [from the discission] was the importance of molecular profiling. At least 20% of these tumors harbor [potentially druggable] molecular alterations, and we need to search for them. If you have the ability to profile the tumor, you should, because you may find [opportunities for targeted treatments] beyond classical cytotoxic chemotherapy that could benefit your patients.
In the case I presented, there was a BRAF mutation, but other tumors may be microsatellite instability–high, have high tumor mutational burden, or harbor RAS mutations. There are now emerging targeted therapies for many of these alterations. We need to continue shifting the field toward a more molecularly driven approach, as I believe our patients will significantly benefit from it.