Background: Microbiome manipulation research is focused on developing techniques to modify the gut microbiome and augment responses to immune checkpoint inhibitors (ICI). Fecal microbiota transplantation (FMT) represents a potential strategy to overcome primary or acquired resistance to ICI. 20 patients with advanced melanoma were enrolled in a phase I multicenter trial to evaluate the safety and response to anti-PD1 combined with FMT using healthy donor stool as first-line treatment (MIMic, NCT03772899 ). Combination therapy was safe, and the objective response rate (ORR) was 65%. We now report survival data based on over 3 years of follow-up. Patients with advanced melanoma and treatment-naïve for advanced disease received a single FMT with healthy donor stool followed by standard anti-PD1 therapy. Progression-free survival (PFS) and overall survival (OS) were measured from the date of FMT to event. Radiographic response was measured using RECIST 1.1 criteria. Both median PFS (mPFS) and median OS (mOS) were determined using the Kaplan-Meier method. Post hoc analyses assessed the impact of specific factors on survival outcomes. Minimum follow-up was 40 months from the date of FMT of the last patient, with the longest surviving patient in complete response at 62.2 months. At the time of data analysis, eight patients were alive and seven patients were without progression. No patients remain on anti-PD1 therapy. Only two patients received additional lines of therapy. The mPFS was 29.6 months and mOS 52.8 months. The 1, 2, and 3 years estimated survival rates were 95%, 74% and 53%, respectively. Post hoc analysis demonstrated significantly improved mPFS in responders and patients with FMT-specific toxicity. Combining first-line anti-PD1 therapy and oral FMT with healthy donor stool in this small cohort was safe and demonstrated an improvement in ORR, mPFS, and mOS, compared with randomized trials. Our sample size was small, and results were only hypothesis generating. The potential benefit of microbiome manipulation using oral FMT from healthy donors prior to ICI in patients with advanced melanoma will be evaluated in the ME.17 randomized phase 2 Canadian study ( NCT06623461 ).

Purpose: To investigate the feasibility of implementing a remote patient monitoring system using an electronic patient-reported outcomes (ePROs) platform in a tertiary cancer center in the Republic of Ireland. Methods: Patients receiving oral chemotherapy and oncology clinicians were invited to participate in the study. Patients were asked to submit weekly symptom questionnaires through an ePRO mobile phone application (app)—ONCOpatient®. Clinical staff were invited to use the ONCOpatient® clinician interface. After 8 weeks all participants submitted evaluation questionnaires. Results: Thirteen patients and five staff were enrolled in the study. The majority of patients were female (85%) with a median age of 48 years (range 22–73). Most (92%) were enrolled over telephone requiring on average 16 minutes. Compliance with the weekly assessments was 91%. Alerts were triggered by 40% of patients who then required phone calls to aid with symptom management. At the end of study, 87% of patients reported they would use the app frequently, 75% reported that the platform met their expectations, and 25% that it exceeded their expectations. Similarly, 100% of staff reported they would use the app frequently, 60% reported that it met their expectations, and 40% that it exceeded their expectations. Conclusions: Our pilot study showed that it is feasible to implement ePRO platforms in the Irish clinical setting. Small sample bias was recognized as a limitation, and we plan to confirm our findings on a larger cohort of patients. In the next phase we will integrate wearables including remote blood pressure monitoring.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers with adenocarcinoma being the most common subtype. Patients with stage IV NSCLC typically have poor prognosis. In these patients, identification of actionable genomic alterations allows for the selection of targeted therapy rather than chemotherapy or chemo-immunotherapy. EGFR mutations are a common oncogenic driver in NSCLC and are targetable by tyrosine kinase inhibitors (TKIs). However, most of the studies primarily focus on common mutations, which are exon 19 deletions (Ex19del) and exon 21 (L858R) point mutations, and there is inconsistent data on efficacy in the treatment of patients with uncommon EGFR mutations. Currently, the first-line treatment for patients with common EGFR mutations involves a third-generation TKI, typically osimertinib. This case describes a 66-year-old gentleman with two uncommon EGFR frameshift deletions (E701fs and L702fs). His tumor staging was denoted as cT3N2M1b, stage IVA. The patient demonstrated a radiological and biochemical response to osimertinib as part of the OCELOT clinical trial (supported by a grant from AstraZeneca), with evidence of tumor marker decline and radiographic improvement within two months of osimertinib treatment initiation. This response has been durable with continued radiological stability and biochemical improvement at 11 months and ongoing. This case will help guide management for patients with this uncommon EGFR mutations and contribute to the scarce literature of EGFR frameshift deletions in advanced NSCLC patients.