The ESMO Breast Cancer 2022 conference held in Berlin, Germany on May 3rd through 5th offered an incredible opportunity to hear the newest research and to discuss the current issues, including future strategies for ensuring better care for patients, and gave MEDSIR the opportunity to share three of our trials with the scientific community: ATRACTIB, CALADRIO and PHERGain.
During the congress we shared the trial design for the ATRACTIB trial which is evaluating the safety and efficacy of first-line atezolizumab in combination with paclitaxel, and bevacizumab in patients with metastatic triple-negative breast cancer (mTNBC).
This international, open-label single-arm, phase II trial is admitting patient ≥18 years old with unresectable locally advanced or mTNBC, ECOG status of 0-1, and who have had no prior systemic therapy in metastatic setting or ≥12 months since (neo)adjuvant taxane-based chemotherapy. Patients are receiving atezolizumab, paclitaxel, and bevacizumab on each 28-day cycle until disease progression, unacceptable toxicity, or patient withdrawal. The ATRACTIB study will assess the investigator-assessed progression-free survival (PFS) as per RECIST v.1.1. as the primary endpoint, with secondary efficacy endpoints including objective response rate (ORR), clinical benefit rate, time to response, duration of response, overall survival, and best percentage change in the sum of the diameters of measurable tumors; safety and tolerability as per NCI-CTCAE v.5.0 will be also analyzed. The study further plans to explore PFS and ORR as per immune-related RECIST and any predictive biomarkers. A safety interim analysis has been performed with the first 20 patients who completed a 3-month follow-up.
The study began October 2020 and is recruiting in Spain, Italy, Portugal, France, Germany, and theUnited Kingdom.
Abstract #221
Abstract Title: ATRACTIB: A Phase II Trial of First Line (1L) Atezolizumab (A) in Combination with Paclitaxel (P) and Bevacizumab (B) in Metastatic Triple Negative Breast Cancer (mTNBC)
The CALADRIO study is an exploratory sub-study of our KELLY trial, which evaluated pembrolizumab and eribulin for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer previously treated with anthracyclines and taxanes.
The study utilized shotgun metagenomic and 16S rRNA gene sequencing to characterize fecal and saliva microbiota profiles, respectively, and microbiota data were analyzed using MEGAHIT, LEfSe, Wilcoxon ranked sum, and PERMANOVA methods. A total of 58 fecal and 68 saliva samples were collected. There was no drug-related microbial toxicity as there was no significant gut or microbial perturbations observed. Bacteroides fragilis in the gut was associated with a clinical benefit, with the most significance at the end of treatment (P=0.0009 by Mann Whitney U test, U = 0, median (yes, no)= 1.95, 0.38 , range = 0–11.73). Patient with a clinical benefit also tended to have a relative abundance of oral Streptococcus of ~40% at baseline, but the difference was lost over time. While these findings need to be validated in larger studies, primary findings suggest Bacteroides fragilis could be a promising biomarker to identify patients who may derive a benefit from this treatment strategy.
Abstract #480
Abstract Title: Gut and oral microbiota profiling in patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC) receiving pembrolizumab (P) plus eribulin (E): CALADRIO
The data from the secondary endpoint from the PHERGain trial, which aimed to determine the most appropriate cutoff for deltaSUVmax (maximum standardized uptake value) in patients with HER2+ early breast cancer treated exclusively with neoadjuvant trastuzumab and pertuzumab, was granted a mini oral abstract.
The results presented showed that the delta SUVmax capability of predicting pathological complete response (pCR) in terms of AUC was 72.1% (95%CI, 65.1-79.2). While the optimal SUVmax reduction cut-off was found to be 77.0%, using this cut-off would classify 32.6% (74 of 227) of patients as FDG-PET responders, increasing the pCR rate from 37.9% (cut-off ≥40%) to 59.5% (44 of 74) of patients (P<0.01). With this optimized cut-off, 19.4% (44 of 227) of patients would achieve a pCR sparing neoadjuvant chemotherapy. These findings suggest that, although increased, the deltaSUVmax cutoff >77% achieves a pCR rate in the range of the control arm, the original cut-off of 40% maximizes the number of patients that can avoid chemotherapy.
The co-primary endpoint 3-year invasive disease-free survival rate from the PHERGain trial should confirm the definitive value of pCR in absence of chemotherapy by adopting an FDG-PET–based strategy.
Abstract #716
Abstract Title: Optimal 18F-FDG PET/CT (FDG-PET) cut-off for pathological complete response (pCR) prediction in HER2-positive [HER2+] early breast cancer (EBC) patients (pts) treated with neoadjuvant trastuzumab (T) and pertuzumab (P) in PHERGain trial
It was a pleasure getting to share these three study with the community and we can’t wait to participate in ESMO Breast Cancer Congress again next year! Please contact us if you want more information about any of the trials we presented and make sure to download the posters!
