Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial.

BACKGROUND: PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC. METHODS: Twenty patients received pembrolizumab and maraviroc (core period, eight cycles), followed by pembrolizumab monotherapy. Primary endpoint was the feasibility rate (patients without treatment-related grade ≥3 immune-related adverse events, treatment-related grade ≥4 adverse events, or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Optional biopsies of liver metastases were performed for analyses of the micromilieu. RESULTS: The feasibility rate was 94.7% [90% CI 77.4-99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68-2.30], median OS 9.83 months [95% CI, 5.59-20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS. CONCLUSIONS: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MMRp CRC patients was limited with prolonged disease stabilizations observed in single patients. Efficacy of poststudy salvage treatment and OS was higher than expected in this heavily pretreated population. THIS TRIAL IS REGISTERED AT CLINICALTRIALS.GOV: NCT03274804.

Completion rate and impact on physician-patient relationship of video consultations in medical oncology: a randomised controlled open-label trial.

BACKGROUND: Mobile phone video call applications generally did not undergo testing in randomised controlled clinical trials prior to their implementation in patient care regarding the rate of successful patient visits and impact on the physician-patient relationship. METHODS: The National Center for Tumour Diseases (NCT) MOBILE trial was a monocentric open-label randomised controlled clinical trial of patients with solid tumours undergoing systemic cancer therapy with need of a follow-up visit with their consulting physician at outpatient clinics. 66 patients were 1:1 randomised to receive either a standard in-person follow-up visit at outpatient clinics or a video call via a mobile phone application. The primary outcome was feasibility defined as the proportion of patients successfully completing the first follow-up visit. Secondary outcomes included success rate of further video calls, time spent by patient and physician, patient satisfaction and quality of physician-patient relationship. FINDINGS: Success rate of the first follow-up visit in the intention-to-treat cohort was 87.9% (29 of 33) for in-person visits and 78.8% (26 of 33) for video calls (relative risk: RR 0.90, 95% CI 0.70 to 1.13, p=0.51). The most common reasons for failure were software incompatibility in the video call and no-show in the in-person visit arm. The success rate for further video visits was 91.7% (11 of 12). Standardised patient questionnaires showed significantly decreased total time spent and less direct costs for patients (Δmean -170.8 min, 95% CI -246 min to -95.5 min), p<0.0001; Δmean -€14.37, 95% CI -€23.9 to -€4.8, p<0.005) and comparable time spent for physicians in the video call arm (Δmean 0.5 min, 95% CI -5.4 min to 6.4 min, p=0.86). Physician-patient relationship quality mean scores assessed by a validated standardised questionnaire were higher in the video call arm (1.13-fold, p=0.02). INTERPRETATION: Follow-up visits with the tested mobile phone video call application were feasible but software compatibility should be critically evaluated. TRIAL REGISTRATION NUMBER: DRKS00015788.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial.

BACKGROUND: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

The second patient? Family members of cancer patients and their role in end-of-life decision making.

BACKGROUND: Family members are important companions of severely ill patients with cancer. However, studies about the desirability and difficulties of integrating relatives in the decision-making process are rare in oncology. This qualitative study explores the family role in decisions to limit treatment near the end of life from the professionals' point of view. METHODS: Qualitative in-depth interviews were conducted with oncologists (n = 12) and nurses (n = 6) working at the Department of Hematology/Oncology at the University Hospital in Munich, Germany. The data were analyzed using a descriptive qualitative methodology and discussed from a medical ethics perspective. RESULTS: Four major themes played a central role in the perception of the medical staff in regard to family members. (1) Family impact on patients' treatment preferences. (2) Strong family wish for further treatment. (3) Emotional distress of the family related to the involvement in end-of-life decision-making. (4) Importance of knowing family structures. CONCLUSIONS: The important role of the family members in patients' disease process is recognized by oncologists and oncology nurses. However, this does not seem to lead to an early involvement of the family members. Developing and establishing a systematic assessment of family members' needs and wishes in order to provide a specific-tailored support should become a priority for interdisciplinary clinical research in the near future.