Tumor lysis syndrome following trastuzumab and pertuzumab for metastatic breast cancer: a case report.

Tumor lysis syndrome is a rare and potentially fatal complication of oncologic treatments, especially in solid tumors. To the best of our knowledge, tumor lysis syndrome has never been reported after trastuzumab and pertuzumab combination therapy. Knowledge of risk factors and active prevention proceedings is of utmost importance to avoid fatal outcomes

Retroperitoneal fibrosis and multiple myeloma: fortuitous association?

We report a 59-year-old man presenting with retroperitoneal fibrosis (RF) associated with IgG lambda multiple myeloma. Recent clinical and immunohistochemical findings suggest that RF might be a particular expression of plasma cell/lymphoid dyscrasia, and that this association is not merely fortuitous. We review the pathophysiological evidence supporting this hypothesis

Seeding of the percutaneous endoscopic gastrostomy site from head and neck carcinoma: case report and review of the literature

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure and is an important supportive treatment for patients with advanced head and neck cancer. Although tumor seeding has been reported in various sites, seeding at the PEG exit site is a rare complication. METHODS AND RESULTS: We describe a clinical case in which squamous cell carcinoma of the hypopharynx implanted at the site of PEG insertion and was successfully removed by surgery. PEG was previously placed by the "pull" technique. A review of the literature, discussion of the mechanism of spread, and recommendations to avoid this complication are discussed. CONCLUSIONS: To avoid this rare and poor prognostic complication, the "pull" technique should be avoided for PEG placement in any patient with head and neck squamous cell carcinoma. An alternative method such as the "push" technique should be preferred

Interim analysis of the AVETUXIRI Trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)—A proof of concept, open-label, nonrandomized phase IIa study.

Background: Immune checkpoint inhibitors have demonstrated poor efficacy in MSS mCRC. Previous research indicate that cetuximab (anti-EGFR chimeric monoclonal antibody) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of anti-PDL1 avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for treatment refractory MSS mCRC. Methods: AVETUXIRI (NCT03608046) is a multicenter academic study recruiting MSS, BRAFV600E wt, mCRC patients (pts) refractory to standard treatment (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) in 2 cohorts (cohort A: RAS wt – cohort B: RAS mut). In both cohorts, patients receive CET (400 mg/m2 W1, 250 mg/m2 W2, 500 mg/m2/2 weeks from W3), IRI (180 - 150 mg/m2/2 weeks from W1) and AVE (10 mg/kg/2 weeks starting from W3). Primary endpoints are overall response rate (ORR), defined as partial or complete response (PR or CR) according (i)RECIST1.1, and safety. Secondary endpoints include disease control rate (DCR), PFS and OS. Based on a Simon 2-stage design for ORR in each cohort (cohort A: P0=0.15, P1=0.33 / cohort B: P0=0.09, P1=0.25 / α = 0.1, β = 0.2 in both cohorts), 10 and 13 patients are required in the first stage of cohort A and B respectively. At least 2 pts have to reach PR or CR in each cohort to allow the continuation of the trial in the 2nd stage. Results: Between Oct 2018 and Jan 2020, 23 patients (median age 62 y-old, 86.9% male 78.3% left-sided, 91.3% synchronous mCRC) have been included in the first stage of the trial. No major or unexpected safety events were observed. 21.7% (5/23) of pts presented grade 3 diarrhea, all related to IRI, with complete resolution after IRI dose reduction or interruption. A reduced starting dose of IRI (150 mg/m2) was amended (09/2019) for the last included 8 pts without any grade 3-4 diarrhea occurrence. Grade 1-2 hypothyroidism was the only immune-related side effect. 3 PR were observed in cohort A and none in cohort B. DCR was 60.0% (6/10) and 61.5% (8/13) in cohort A and B respectively. Median PFS and OS were respectively 4.2 and 12.7 months (cohort A) and 3.8 and 14.0 months (cohort B). 6 months-PFS rate was 40.0% and 38.5% in cohort A and B. 12 months-OS rate was 53.3% and 57.7% in cohort A and B. The median follow-up of patients was 9.2 months. Conclusions: The AVETUXIRI trial met its primary efficacy endpoint for RAS wt mCRC pts justifying the study continuation in cohort A (2nd stage). No PR was observed in RAS-mut cohort. Nevertheless, encouraging data of DCR, PFS and OS observed in RAS mut cohort allow the opening of a new cohort for RAS-mut mCRC (cohort C) with PFS as primary endpoint. Clinical trial information: NCT03608046

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer: a 13 years-retrospective monocentric study.

BACKGROUND AND STUDY AIM: Over the last 20 years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has progressively become a therapeutic option for peritoneal carcinomatosis thanks to its favourable oncologic results. The aim of this study is to analyse the overall survival and recurrence-free survival, after complete CRS and closed abdomen technique HIPEC for peritoneal carcinomatosis from colorectal cancer. PATIENTS AND METHODS: This retrospective study collected the data from all patients who underwent a CRS with HIPEC for colorectal cancer at "Cliniques universitaires Saint Luc" from October 2007 to December 2020. Ninety-nine patients were included. RESULTS: The median follow-up was 34 months. Post-operative mortality and Clavien-Dindo grade III/IV morbidity rates were 2.0% and 28.3%. The overall 2-year and 5-year survival rates were 80.1% and 54.4%. Using the multivariate analysis, age at surgery, liver metastases and PCI score >13 showed a statistically significant negative impact on overall survival. The 2-year and 5-year recurrence-free survival rates were 33.9% and 22%. Using the multivariate analysis, it was found that liver metastases, the extent of carcinomatosis with PCI>7 have a statistically significant negative impact on recurrence-free survival. CONCLUSIONS: Despite a high recurrence rate, CRS followed by HIPEC to treat peritoneal carcinomatosis from colorectal origin offer encouraging oncologic results with a satisfying survival rate. When PCI>13, CRS and HIPEC does not seem to offer any survival benefit and to efficiently limit recurrence, our data are in favor of a maximum PCI of 7

Homogeneity of pathological response (PR) and histopathological growth pattern (HGP) in resected colorectal liver metastases (CRLM) are associated with favorable survival outcome after surgery.

Background: Surgical resection of CRLM aims to maximize patient survival. However, recurrence rates remain high post-surgery. We previously reported the prognostic relevance of tumor regression grading (TRG) and HGP of resected CRLM. Several studies reported the association of tumoral heterogeneity with anti-cancer drug resistance and prognosis. This study aims to explore tumoral heterogeneity for TRG and HGP in patients resected for CRLM and its prognostic implication. Methods: Tumor homogeneity for PR and HGP was evaluated in 2 independent cohorts. Cohort 1 included 57 patients (159 CRLMs) resected after chemotherapy/bevacizumab (prospective BEV-ONCO trial). Cohort 2 included 221 patients (582 CRLMs) operated after preoperative treatment or not. TRG (1 to 5 according complete to no response), HGP (desmoplastic, pushing, replacement or mixed) were evaluated for each CRLM. Max-TRG (higher TRG among all the CRLM) was used to define PR. Homogenous TRG (TRG-h) and HGP (HGP-h) was defined when all CRLMs had the same TRG or HGP pattern. HGP homogeneous desmoplastic (HGP-hd) was defined when all CRLM had a desmoplastic HGP. TRG-h, HGP-h and HGP-hd were combined into a homogeneity score (H-score: 0 to 3, 1 point given for each parameter and summed-up). Overall survival (OS for both cohorts), progression-free survival (PFS for cohort 1) and time to relapse (TTR for cohort 2) were estimated using the Kaplan–Meier method and compared by log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. Results: Patient and disease characteristics were comparable in both cohorts excepted for preoperative treatment. In cohort 1, TRG-h and HGP-h were significantly associated with a longer PFS (HR = 0.21; 95CI:0.10-0.43, p < 0.001; HR = 0.27; 95CI = 0.14-0.54, p < 0.001) and better OS (HR = 0.23; 95CI = 0.07-0.70, p = 0.010; HR = 0.32; 95CI = 0.10-0.93, p = 0.037). Interestingly, the same significant results were observed in cohort 2 for TTR (TRG-h: HR = 0.60; 95CI = 0.43-0.85, p = 0.004; HGP-h: HR = 0.68; 95CI = 0.49-0.94, p = 0.017) and OS (TRG-h: HR = 0.51;95CI = 0.33-0.80, p = 0.003; HGP-h: HR = 0.63; 95CI = 0.41-0.97, p = 0.034). HGP-h reported a significant association with TRG-h, a Max-TRG < = 3, the absence of HGP replacement and mixed, a desmoplastic pattern, and the absence of sinusoidal obstruction syndrome in both cohorts. H-score was significantly associated with TTR (score 1-2: HR = 0.57; 95CI = 0.38-0.85, p = 0.004; score 3: HR = 0.4; 95CI = 0.24-0.64, p < 0.001) and OS (score 3: HR = 0.31; 95CI = 0.15-0.64, p < 0.001) in univariate analysis and with OS (HR = 0.74; 95CI = 0.59-0.94, p = 0.011) in multivariate analysis (cohort 2). Conclusions: TRG-h and HGP-h are strongly associated with patient’s survival. H-score could be an easy morphological and prognostic score to assess. Validation studies are needed

599P R-IMMUNE: A phase Ib/II study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with locally advanced rectal cancer (LARC)

BACKGROUND : There is a strong rationale to combine radiotherapy with immune checkpoint inhibitors (ICIs). This study evaluates this combination before surgery in locally advanced rectal cancer (LARC). [...

635P Avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): The AVETUXIRI phase II study

BACKGROUND : Cetuximab could mediate, independently from RAS mutation, an immunogenic tumor cell death and antitumor immune response. This trial explores the efficacy and safety of AVE, CET and IRI for the treatment of refractory MSS mCRC. [...

2237P Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Translational analyses of the AVETUXIRI phase II trial

BACKGROUND : This trial explores the clinical efficacy and safety of AVE, CET and IRI for treatment refractory MSS mCRC. We aim at characterizing the immune response for biomarker discovery through associated translational research. [...

Interim analysis of the phase II AVETUXIRI trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Background: Immune checkpoint inhibitors demonstrated poor efficacy in MSS mCRC. Cetuximab (anti-EGFR inhibitor) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of avelumab (anti-PDL1) combined with cetuximab and irinotecan for treatment refractory MSS mCRC and to understand its mechanisms of action through associated translational research. Methods: AVETUXIRI trial (NCT03608046) enrols MSS, chemorefractory (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) mCRC patients in 2 cohorts (A: RAS-wt, n = 10 – B: RAS-mut, n = 13). Primary endpoints are safety and tumor response rate ((i)RECIST1.1). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). According to a Simon 2-stage design, 23 patients have been included in the first stage of the trial. Multiplex immunofluorescence and RNA sequencing were realized on metastasis biopsies performed before, during and after the treatment. Densities of CD3+ (T cells) and CD8+ (cytotoxic) were quantified and analyzed with to generate an immunoscore (IS). RNA-seq data was used to perform differential expression analysis (DESeq2), gene set enrichment analysis (GSEA), deconvolution analysis (ConsensusTME) and gene ontology analysis (GO). Results:: No unexpected safety signals were observed. 3/10 tumor responses were observed in cohort A, 0/13 in cohort B. DCR was 60.0% and 61.5% in cohort A and B, respectively. 6-months PFS and 12-months OS rates were respectively 40.0% and 50.0% (cohort A) and 38.5% and 46.2% (cohort B). Independently of RAS mutation, patients with a high IS (metastasis biopsy, baseline) had significantly higher tumor shrinkage (OR = 18.67 p = 0.019), median PFS (6.9 vs 3.4 months; HR = 0.16, p = 0.002) and median OS (13.7 vs 7.9 months, HR = 0.26, p = 0.009). Similarly, tumor shrinkage and survival outcome (PFS > 6 months, OS > 12 months) were associated with upregulation of an adaptive immune response signature (including Th1, chemokine, adhesion molecules, immune checkpoints and T-cell activation genes, p. adj = 0.009) and the GSEA hallmark of epithelial to mesenchymal transition (p. adj = 0.045). Few modifications of IS and gene expression profiles were observed on the different metastasis biopsies performed overtime in the included patients. Conclusions: AVETUXIRI met its preliminary primary efficacy endpoint for RAS-wt mCRC pts, justifying its current continuation. Encouraging survival data observed in RAS-mut cohort allow the opening of a new cohort (PFS as primary endpoint). IS and adaptive immune response signature evaluated on metastases biopsies were associated with treatment efficacy and survival