Bobbie J. Rimel, MD, Isabelle L. Ray-Coquard, MD, PhD, on Cervical Squamous Carcinoma: Neoadjuvant Nivolumab Plus Ipilimumab
2023 ASCO Annual Meeting
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Isabelle L. Ray-Coquard, MD, PhD, of Centre Léon Bérard and the University Claude Bernard Lyon Est, discuss findings from the COLIBRI trial, which showed that, for patients with cervical squamous cell carcinoma, neoadjuvant nivolumab plus ipilimumab is safe and orchestrates de novo immune responses. The 82.5% complete response rate for primary tumors 6 months after standard chemoradiation therapy suggests favorable clinical outcomes (Abstract 5501).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Good morning, Dr. Ray-Coquard. Thank you so much for joining me today, and congratulations on the COLIBRI study. Would you mind telling me a little bit about the design of the study, and how you chose to sequence the drugs this way?
Thank you so much to learn about COLIBRI trial. We are very exciting by such trial. As you understand, it's not a trial dedicated to change routine practice, but to understand what's happened when we use immunotherapy in cervical cancer, and more particularly in locally advanced cervical cancer. The idea is really to explore the double checkpoint inhibition, nivolumab plus ipilimumab, just before to start standard radio chemotherapy.
Then to use a six months of maintenance therapy, to continue to include an immune response after radiotherapy. We would like, really, to understand two points. Our double checkpoint inhibition is able to change something in the micro environment of cervical cancer, and e-sequencing immunotherapy and radiotherapy can be better. That what we have seen, particularly with the results of the CALLA trial.
Yeah. I think it's really striking, in the trial, that despite having a neoadjuvant immunotherapy section, that everyone was able to receive radiation, and there were no significant toxicities. Were you surprised by the safety profile of the trial?
I would say no, because we try to work a lot before, and we just include one cycle of ipilimumab before radiotherapy, that it is, I'm thinking, totally easy. The safety profile right now, as you mentioned, is very good. Also, during the RTCT, and after, during the maintenance therapy, we see very few treatment related that adverse event. For sure, we need to wait for more long follow-up, to be sure about what we are seeing today, but the first signal is very good. The other point is that starting immunotherapy before radiotherapy, during these months, did not change anything. We see six patients, in partial response, after one month of immunotherapy. It's something really interesting for the patients.
Very interesting for the patients. I noticed that there were about 25% of patients, who had a planned secondary biopsy, that were unable to undergo that biopsy. The reason cited was that they were concerned about having undergoing a painful procedure. Since this is such a critical translational endpoint, what are your thoughts for future studies about how to encourage, or help, patients participate in these critical biopsies?
I'm not sure I will move in this setting in the future, for two reasons. You're right. Painful process never do to be proposed to the patient. What we have seen right now, in COLIBRI, is that on the 27 tumor biopsy we obtain, there is no tumor cell for 26. That mean that, probably, this biopsy, just after RTCT, is not so interesting. What we are doing, right now, we are correlating the systemic immune response and the results. If we are able to correlate immune systemic response, for the future, we will continue with blood sample, and we definitively avoid this biopsy just after RTCT, because of the painful process.
Understood. Where do you think this data is going to fit, in the design of future, larger studies?
I'm sure. I'm sure, because what we have report with the COLIBRI trial is that it is safe, acceptable for the patient, easy to run. I'm pretty sure that it is the good model for the researcher, the clinician, but also the pharma company, to move in such design, where we would like to explore, which could be the best combination of the best drug we have to explore in cervical cancer. I hope that this kind of trial, we will be very helpful to win time, and also to avoid the huge issue that we have when we include more than 400 patients in a Phase 3, with at the end we see negative results. It is really, the key message of this trial, we can do better, shorter, and easy for the patient.
I think you're making some excellent points. Thank you so much for joining me today, and congratulations on your trial.
Thank you very much.
Bradley J. Monk, MD, of the University of Arizona, Phoenix, and Creighton University, discusses phase III findings from the KEYNOTE-826 study of overall survival results in patients with persistent, recurrent, or metastatic cervical cancer. Study participants received first-line treatment of pembrolizumab plus chemotherapy, with or without bevacizumab, which reduced the risk of death by up to 40% in three different subsets of patients (Abstract 5500).
Thierry Conroy, MD, of the Institut de Cancérologie de Lorraine, discusses phase III findings from the PRODIGE 23 trial, showing that neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy, surgery, and adjuvant chemotherapy improved all outcomes, including overall survival, in patients with locally advanced rectal cancer compared with standard chemoradiotherapy, surgery, and adjuvant chemotherapy (Abstract LBA3504).
Alberto Bossi, MD, of Institut Gustave Roussy, discusses phase III findings showing that combining prostate radiotherapy with systemic treatment did not improve overall survival in men with de novo metastatic castration-sensitive prostate cancer and low metastatic burden. However, best outcomes (radiographic progression–free-survival and overall survival) were observed in men receiving the standard of care plus abiraterone acetate plus prednisone with radiotherapy (Abstract LBA5000).
Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Thejus Jayakrishnan, MD, of the Cleveland Clinic Taussig Cancer Institute, discuss significant differences in the citrate cycle, a core pathway of cellular metabolism associated with colorectal cancer. Metabolomic differences impacted by environmental exposures (arginine biosynthesis and dietary red meat) were also noted, suggesting possible links with younger age of onset in this disease (Abstract 3510).
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, and Gregory Roloff, MD, of the University of Chicago, discuss data that are the first to demonstrate post–FDA approval efficacy and toxicity rates of brexucabtagene autoleucel in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Although the data may confirm high response rates associated with this agent, they also highlight the need for interventions to reduce associated toxicities (Abstract 7001).