First-line Metastatic Patients Research Articles

A 14-year retrospective of HER2 + metastatic breast cancer treatment at one comprehensive cancer center: Impact of the trastuzumab/pertuzumab and trastuzumab-emtansine sequence versus trastuzumab on overall survival.

Introduction: Monoclonal antibodies represent a significant improvement in the treatment of the HER2 + metastatic cancer, which is associated with a worse prognosis. The objective of this study was to compare overall survival (OS) data in patients treated with trastuzumab + pertuzumab followed by trastuzumab-emtansine (T-DM1) in the second line of metastatic treatment (Arm A) versus patients treated with trastuzumab alone (Arm B). Progression-free survival (PFS) in first-line metastatic patients was also compared in both arms. Methods: This single-center retrospective study included patients from February 2008 to August 2022. OS and PFS of both arms were described and estimated using the Kaplan-Meier method. Data were extracted from electronic medical records and CHIMIO prescribing software. Results: The total duration of metastatic treatment of the 82 patients was significantly longer in the arm A (43.2 ± 28 months vs 33.6 ± 28.9 months), as was the median time to death (59 vs 52 months). The OS data showed a significant reduction in the risk of death in the arm A (Hazard Ratio = 0.59; 95% Confidence Interval [0.37-0.94]; p = 0.02). No difference was shown for PFS. Conclusion: The trastuzumab/pertuzumab/T-DM1 combination showed a significant improvement in OS. Our results are in line with the CLEOPATRA and EMILIA studies, but long-term responders in the arm A may have impacted our results. The absence of difference in term of PFS in first metastatic line may be explained by a selection bias, as patients in the arm A potentially have more aggressive forms.

Occurrence and characteristics of patients with de novo advanced breast cancer according to patient and tumor characteristics – A retrospective analysis of a real world registry

BackgroundPatients with de novo metastatic breast cancer (dnMBC) may have different clinical and pathological characteristics. In studies concerned with first-line metastatic patients, the proportion of these patients without secondary resistance mechanisms may have a large influence ont the study results. The aim of this study was to identify patient and tumor characteristics that are associated with dnMBC vs. recurrent MBC (rMBC). MethodsThis is a retrospective analysis of data prospectively collected in the PRAEGNANT metastatic breast cancer registry (NCT02338167). Firs line treated patients were eligible. Patient and tumor characteristics were compared with common disease and tumor characteristics relative to de novo metastatic status, as well as early and late recurrences after primary disease without metastases. ResultsAmong the 947 patients identified, 355 were included with de novo metastatic disease (37.5%). Older age and HER2-positive disease were significantly associated with a higher frequency of dnMBC. Patients younger than 50, 50–69, or 70 years or older had dnMBC frequencies of 22.7%, 44.0%, and 57.6%, respectively. HER2-positive patients had dnMBC at initial presentation in 49.1% of cases, in comparison with 21.9%, 35.5%, and 37.6% in patients with triple-negative, luminal A–like and luminal B–like breast cancer, respectively. ConclusionAge and breast cancer subtype are associated with the frequency of first-line MBC patients. Inclusion criteria concerning age or breast cancer subtype can influence the frequency of these patients in a selected patient population and can therefore modify the number of patients with secondary resistance to specific therapies in clinical trials.

Abstract IA-08: Clinical advances in pancreas adenocarcinoma

Abstract IA-08: Clinical advances in pancreas adenocarcinoma

Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay

ABSTRACTMonitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFα production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNγ production by NK cells in response to either Type-I IFN or TLR7/8 ligand, and (iii) a coordinated impairment of cytokine (IL-2, IFNγ, IL-21) production by T cell subpopulations. Overall, these alterations are further accentuated according to the stage of the disease in first-line metastatic patients. Finally, whereas we did not detect functional modification of DC subsets in response to TLR7/8 ligand, we highlighted increased IL-12p40 production by monocytes specifically at first relapse (FR). Our results reinforce the importance of monitoring both innate and adaptive immunity to better evaluate dysfunctions in cancer patients and suggest that our whole-blood assay will be useful to monitor response to treatment, particularly for immunotherapeutic strategies.