Michael Cecchini, MD, is an associate professor of medicine (medical oncology) at Yale School of Medicine; as well as the co-director of the Colorectal Program in the Center for Gastrointestinal (GI) Cancers, the medical oncology section lead for the National Accreditation Program for Rectal Cancer, the co-director of the GI Clinical Research Team, and a phase 1 investigator at Yale Cancer Center

Dr Cecchini on the Efficacy of Neoadjuvant Chemotherapy in CRC Liver Metastases

Michael Cecchini, MD, an associate professor of medicine (medical oncology) at Yale School of Medicine; as well as the co-director of the Colorectal Program in the Center for Gastrointestinal (GI) Cancers, the medical oncology section lead for the National Accreditation Program for Rectal Cancer, the co-director of the GI Clinical Research Team, and a phase 1 investigator at Yale Cancer Center, discussed findings from a study evaluating the clinical significance of neoadjuvant chemotherapy on levels of tumor-infiltrating lymphocytes in patients with colorectal cancer (CRC) with liver metastases.

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Michael Cecchini, MD, discusses the effects of neoadjuvant chemotherapy on tumor-infiltrating lymphocyte levels in colorectal cancer with liver metastases.

Dr Cecchini on Etrumadenant-Based Combinations in Previously Treated mCRC

Michael Cecchini, MD, associate professor, medicine (medical oncology), co-director, Colorectal Program, Center for Gastrointestinal Cancers, medical oncology section lead, National Accreditation Program for Rectal Cancer, Internal Medicine, co-director, GI Clinical Research Team, Yale School of Medicine, discusses findings from the ARC-9 trial (NCT04660812) investigating an etrumadenant (AB928)–based combination regimen in patients with previously treated metastatic colorectal cancer (mCRC).

Cohort B of ARC-9 randomly assigned patients with mCRC to receive etrumadenant plus zimberelimab (AB122), mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), and bevacizumab (Avastin; n = 75) or regorafenib (Stivarga; n = 37). This trial yielded efficacy findings unlike any that have been seen in a randomized clinical trial of mCRC in the third-line setting, Cecchini begins. The study met its primary end point of progression-free survival (PFS). At a median follow-up of 20.4 months, the median PFS was 6.24 months (95% CI, 5.49-7.52) with the etrumadenant regimen vs 2.07 months (95% CI, 1.84-2.96) with regorafenib (HR, 0.27; 95% CI, 0.17-0.43; 

 < .001). The 6-month PFS rates in the etrumadenant and regorafenib arms were 54% and 6%, respectively. The 12-month PFS rates in these respective arms were 16% and 3%. This PFS benefit with etrumadenant vs regorafenib was observed across all analyzed patient subgroups, including geographic region, baseline ECOG performance status, baseline liver metastasis status, primary diagnosis, and primary tumor location.

Additionally, the median overall survival (OS) was 19.68 months (95% CI, 14.69-20.60) in the investigational arm vs 9.49 months (95% CI, 7.95-12.52) in the control arm (HR, 0.37; 95% CI, 0.22-0.63; 

 < .001). The 6-month OS rates in the etrumadenant and regorafenib arms were 90% and 71%, respectively. The 12-month PFS rates in these respective arms were 64% and 34%. The median OS was consistently longer in the etrumadenant arm vs the regorafenib arm across all analyzed subgroups.

The confirmed overall response rate was 17.3% in the etrumadenant arm vs 2.7% in the regorafenib arm. The median duration of response with etrumadenant was 11.5 months.

Michael Cecchini, MD, discusses findings from the ARC-9 trial investigating an etrumadenant-based combination in patients with previously treated mCRC.

Dr Cecchini on the Initial Efficacy of CM24 Plus Nivolumab and NALIRIFOX in Advanced PDAC

Michael Cecchini, MD, assistant professor, medicine, Medical Oncology, co-director, Colorectal Program, the Center for Gastrointestinal (GI) Cancers, Yale School of Medicine, medical oncologist, Yale Medicine, discusses interim efficacy and safety data from the phase 2 FW-2020-01 study (NCT04731467) in advanced/metastatic pancreatic ductal adenocarcinoma (PDAC).

The global multicenter, open-label, randomized study evaluated the novel CEACAM1-targeted monoclonal antibody CM24 with nivolumab (Opdivo) and liposomal irinotecan, 5-fluorouracil, and leucovorin (NALIRIFOX) vs NALIRIFOX alone in patients with advanced/metastatic PDAC following progression on or during first-line therapy, Cecchini begins.

, results from the trial demonstrated significant improvements in progression-free survival (PFS), overall survival (OS), and response rates with the addition of CM24 and nivolumab to the NALIRIFOX regimen in the second-line treatment setting, he reports. The median OS was 7.72 months (95% CI, 4.00-8.11) with the experimental regimen compared with 5.62 months (95% CI, 3.22-7.89) in the control arm, Cecchini details. This resulted in a hazard ratio of 0.74 (95% CI, 0.31-1.77), translating to a 26% reduction in the risk of death or disease progression.

Furthermore, the median PFS was doubled from 1.9 months (95% CI, 1.8-5.0) in the control arm to 3.8 months (95% CI, 0.9-3.6) in the investigational arm, with a hazard ratio of 0.72 (95% CI, 0.33-1.60), corresponding to a 28% reduction in the risk of death or progression, Cecchini adds. Response rates were significantly higher in the investigational arm at 25% vs 6.7% in the control arm, and the disease control rate was 62.5% vs 40.0% with the experimental vs control regimens, respectively. This showed that all efficacy measures favored the investigational regimen, Cecchini explains.

The addition of CM24 to nivolumab and NALIRIFOX was also well tolerated. The interim analysis suggests that the combination of CM24, nivolumab, and NALIRIFOX has a manageable safety profile and offers longer PFS, supported by higher objective response rates (ORR) and disease control rates (DCR). OS data continue to mature with further analyses.

The combination therapy could represent a promising second-line treatment option for patients with advanced/metastatic PDAC.

Michael Cecchini, MD, discusses interim data on the use of CM24 with nivolumab and NALIRIFOX in advanced/metastatic pancreatic ductal adenocarcinoma.


Michael Cecchini, MD, assistant professor, medicine, Medical Oncology, co-director, Colorectal Program, the Center for Gastrointestinal (GI) Cancers, Yale School of Medicine, medical oncologist, Yale Medicine, discusses the phase 3 PROSPECT trial (NCT01515787) of neoadjuvant chemoradiation vs neoadjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy with selective use of chemoradiation, followed by total mesorectal excision in patients with locally advanced rectal cancer, and how this regimen may fit into the current treatment landscape for rectal cancer.

Data from the randomized trial were presented at the 2023 ASCO Annual Meeting, showing that neoadjuvant FOLFOX with the selective use of chemoradiation is safe and effective in the treatment of patients with T2 node-positive, T3 node-negative, or T3 node-positive rectal cancer. The PROSPECT trial was presented during the plenary session at the meeting and was a non-inferiority study conducted by the Alliance for Clinical Trials in Oncology with 1128 patients treated, Cecchini begins.

The main goal of the study was to compare outcomes of completing induction chemotherapy vs chemoradiotherapy in rectal cancer, he expands. The induction chemotherapy group underwent an evaluation to understand whether chemoradiation, the typical standard of care for this patient population, could be omitted, he says. Investigators evaluated the possibility of de-escalating current therapies for patients with low-risk, mid-to-high rectal cancer. This long effort focused on quality of life for this patient group, Cecchini emphasizes. Upon asking whetheroncologists can give less intensive treatment for these patients, PROSPECT showed no compromise in efficacy with the omission of radiation therapy in this population, Cecchini explains.

Although Cecchini shares that this is an exciting finding, he stresses that the treatment of rectal cancer has changed dramatically over the past 10 years. Now, oncologists are using total neoadjuvant therapy in the majority of patients, and for some patients, a‘watch-and-wait’ approach is more beneficial. Therefore, these updated data may be challenging to incorporate into clinical practice, Cecchini continues. However, they show that for patients with locally advanced rectal cancer, radiation can safely be omitted, Cecchini concludes.

Michael Cecchini, MD, discusses the phase 3 PROSPECT trial of neoadjuvant chemoradiation vs neoadjuvant fluorouracil, leucovorin, and oxaliplatin chemotherapy with selective use of chemoradiation, followed by total mesorectal excision in patients with locally advanced rectal cancer, and how this regimen may fit into the current treatment landscape for rectal cancer.


Michael Cecchini, MD

Articles

Dr Cecchini on the Efficacy of Neoadjuvant Chemotherapy in CRC Liver Metastases

Dr Cecchini on Etrumadenant-Based Combinations in Previously Treated mCRC

Dr Cecchini on the Initial Efficacy of CM24 Plus Nivolumab and NALIRIFOX in Advanced PDAC

Dr Cecchini on the Results of the PROSPECT Trial in Rectal Cancer