Dual Checkpoint Inhibition with Ipilimumab plus Nivolumab After Progression on Sequential PD‐1/PDL‐1 Inhibitors Pembrolizumab and Atezolizumab in a Patient with Lynch Syndrome, Metastatic Colon, and Localized Urothelial Cancer

We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD‐L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA‐4) and nivolumab (targeting PD1). Over a 28‐month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR‐deficient CRC may experience meaningful clinical benefit from multiple sequential ICB regimens, a strategy that can be further tested in clinical trials.Key Points.The case exemplifies clinical benefit from sequential immune checkpoint blockade in a patient with Lynch syndrome with advanced metastatic colorectal cancer and urothelial cancer.Metabolic response, with decreased fluorodeoxyglucose avidity on positron emission tomography and computed tomography, and reductions in tumor markers, such as carcinoembryonic antigen, were helpful in this case to monitor disease status over a 28‐month period of therapy.The concept of sequential immune checkpoint blockade in patients with advanced mismatch repair‐deficient cancer merits further study to determine which patients are most likely to benefit.
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine Clinic: Molecular Tumor Board, Gastrointestinal Cancer Precision Medicine Clinic: Molecular Tumor Boards Source Type: research

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Conclusions: Our results suggest that transcriptional patterns are indicative for TMM pathway activation with subtle differences between TEL and ALT mechanisms in a CRC subtype-specific fashion. Sequencing data potentially provide a suited measure to study alterations of telomere length and of underlying transcriptional regulation. Further studies are needed to improve this method.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsSporadic dMMR breast cancers are extremely rare (Davies et al. in Cancer Res 77:4755 –4762, 2017). It seems reasonable to conclude that identifying a dMMR breast cancer in a patient with known LS strongly suggests that her LS is breast cancer-predisposing. LS patients with dMMR breast cancers might therefore be considered for above-average breast cancer screening for the developme nt of additional breast cancers. Also, the FDA recently granted approval of checkpoint inhibitor therapy for all metastatic dMMR solid malignancies (Lemery et al. in N Engl J Med 377:1409–1412, 2017). MMR expression assays ...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
AbstractBackgroundWe previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.MethodsThe Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Onlypath_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
ConclusionsResults of the Idylla ™ MSI Assay were highly concordant with results of routine tests and lower failure rates were observed. Further advantages are the lack of need for matched normal tissue, the low dependence on pre-analytical conditions, the simplified workflow, the short turnaround times, the automated result inte rpretation, and the very limited hands-on work.Editorial acknowledgementTeams involved in the MSI, Idylla MSI Assay, Colon Rectal Cancer, Multicenter Study.Legal entity responsible for the studyIrblleida.FundingBiocartis.DisclosureX. Matias-guiu: Non-remunerated activity/ies: Biocartis.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD-L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA-4) and nivolumab (targeting PD1). Over a 28-month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR-defici...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Abstract Colorectal cancer (CRC) is one of the most common causes of cancer mortality in the world. The incidence is related to increases with age and western dietary habits. Early detection through screening by colonoscopy has been proven to effectively reduce disease-related mortality. Currently, it is generally accepted that most colorectal cancers originate from adenomas. This is known as the "adenoma-carcinoma sequence", and several studies have shown that early detection and removal of adenomas can effectively prevent the development of colorectal cancer. The other two pathways for CRC development ...
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
ConclusionConcordance of opinion among GCs for the management of patients with negative genetic test results exists when FDRs are affected. However, when affected relatives are more distant, GCs disagreed on screening recommendations. These data suggest a need for guidelines for patients with a family history of cancer and a negative genetic test.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
ConclusionsThe ‘pelvis-first’ approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
AbstractLynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1,MSH2,MSH6, andPMS2) encoding mismatch repair proteins. Being located immediately upstream of theMSH2 gene,EPCAM abnormalities can affectMSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replica...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
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