Sebastian Stintzing, MD, on Colorectal Cancer: Influence of Liquid Biopsy in First-Line Combination Treatment

2023 ASCO Annual Meeting


Sebastian Stintzing, MD, of the Charité Universitätsmedizin Berlin, discusses results from the phase III FIRE-4 study, which showed that liquid biopsy is clinically relevant in verifying mutational status in patients with metastatic colorectal cancer and is efficacious in first-line treatment of FOLFIRI and cetuximab for patients with RAS wild-type disease (Abstract 3507).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The purpose of the FIRE-4 study was to test whether a switch maintenance from an anti-EGFR containing regimen first-line to bevacizumab plus [inaudible 00:00:19] would prevent upcoming RAS mutations as secondary resistant factors and therefore prolong progression-free survival over the median time that is reached with the standard treatment of FOLFIRI plus cetuximab. Therefore, we randomized 672 patients in either FOLFIRI plus cetuximab until progression or intolerable toxicity versus FOLFIRI cetuximab up to eight and 12 cycles, and then switch maintenance towards [inaudible 00:00:52] and bevacizumab. Primary endpoint of the first line treatment was PFS and we have published this in last year, we did not reach a PFS. PFS of both arms was comparable. At this ASCO, we present the data of the liquid biopsy translational program. We took liquid biopsies at the beginning, at baseline, at the 6 to 12 cycles within treatment. And then at the end of the treatment, at progression. What was quite unexpected, this was a RAS wide type population by tissue-based testing within the liquid biopsy, we were able to find 13% of patients having a RAS mutation at baseline. And the outcome of those patients were as expected for RAS mutant patients. At PFS of roundabout nine months and overall survival of 22 months, whereas the double Y type population, the RAS and BUFY type population exceeded the PFS with 11.5 months and then overall exceeding in median 33 months. We also had the on treatment measurement of liquid biopsy and was quite interesting. It took in median 48 weeks until the RAS mutation came up in those patient treated continuously with anti-EGFR treatment. Almost after one year of treatment, there were upcoming RAs mutations and we found those in round about 19%. One out of five patients got to this RAS mutation. It did not impact overall survival. What are our conclusions here? First of all, baseline liquid biopsy is important to find the right patient population and to sort out those patient who may have a RAS wide type tumor by tissue-based analysis, but a RAS mutant tumor by liquid biopsy because those patients do not derive benefit from anti-EGFR treatment. At baseline it's important, it's meaningful. During treatment, we think there's no meaning for the RAS testing by liquid biopsy because those patients who actually got a RAS mutation during treatment have a very long treatment time, are on treatment for almost a year. And it has no impact on overall survival. What would be the next steps? In my opinion, we should do a liquid biopsy in our clinical practice before starting anti-EGFR treatments or at baseline to cover tumor heterogeneity and to cover the real RAS mutational status of our patients that we want to treat. B, I think it'll be important to find a threshold during treatment where we can apply treatment holidays. Where's the threshold? How far can we actually treat the patients? How far can we shrink down the tumor volume until it is safe to say, okay, now we can do a treatment holiday, just to give the patient a break and from a patient perspective to have a better quality of life during this treatment course.

Related Videos


Tycel J. Phillips, MD, and Alex F. Herrera, MD, on Classical Hodgkin Lymphoma: New Data on Nivolumab, AVD, and Brentuximab Vedotin

Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).

Gynecologic Cancers

Bobbie J. Rimel, MD, and Mansoor R. Mirza, MD, on Endometrial Cancer: Patient-Reported Outcomes With Dostarlimab, Carboplatin, and Paclitaxel

Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Mansoor R. Mirza, MD, of Denmark’s Rigshospitalet and Copenhagen University Hospital, discuss new findings on dostarlimab-gxly plus carboplatin/paclitaxel, which improved progression-free survival while maintaining health-related quality of life, further supporting its use as a standard of care in primary advanced or recurrent endometrial cancer (Abstract 5504).

Skin Cancer

Shailender Bhatia, MD, on Merkel Cell Carcinoma: Results From CheckMate 358 on Nivolumab With or Without Ipilimumab

Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, discusses phase I/II results on the efficacy of nivolumab with or without ipilimumab in patients with recurrent or metastatic Merkel cell carcinoma. The study found that, for this rare and aggressive skin cancer, nivolumab showed clinical activity in advanced disease. However, these results from CheckMate 358 do not suggest an additional benefit with ipilimumab added to nivolumab (Abstract 9506).



Claire Roddie, PhD, MBChB, on B-ALL: Safety and Efficacy Data of Obecabtagene Autoleucel

Claire Roddie, PhD, MBChB, of University College London, discusses results of the FELIX study, which showed that the second-generation chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel is safe for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, even those with a high burden of disease. This agent yielded high rates of complete response and ongoing CAR T-cell persistence in most patients whose disease responded (Abstract 7000).

Skin Cancer

Allison Betof Warner, MD, PhD, and Zeynep Eroglu, MD, on Metastatic Melanoma: New Data on Dabrafenib, Trametinib, and Navitoclax

Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Zeynep Eroglu, MD, of H. Lee Moffitt Cancer Center and Research Institute, discusses phase II findings showing that in patients with BRAF-mutant metastatic melanoma, dabrafenib plus trametinib and navitoclax (DTN) was associated with a complete response rate of 20% and an overall response rate of 84%. Additionally, there was a trend toward improved overall survival in patients treated with DTN compared with dabrafenib plus trametinib alone; the difference in overall survival was more pronounced in patients with a smaller tumor burden (Abstract 9511).