Phase 2 study of pembrolizumab in patients with advanced rare cancers

Background Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers. Methods In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR). Results A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma–pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug. Conclusions The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma–pheochromocytoma supports further evaluation of pembrolizumab in this patient population. Trial registration number NCT0272173

Role of appendectomy at the time of primary surgery in patients with early-stage ovarian cancer

To determine whether appendectomy is warranted in patients with apparent early-stage ovarian cancer who undergo surgery for staging and cytoreduction and to determine the complication rate associated with appendectomy in such patients. We reviewed the medical records of all patients who underwent appendectomy at the time of primary surgery for ovarian cancer at The University of Texas M. D. Anderson Cancer Center between January 1992 and December 2004 and who did not meet any of the following exclusion criteria: stage III or IV ovarian cancer, appendectomy as part of a second-look procedure or secondary tumor-reductive surgery, primary appendiceal cancer, primary gastrointestinal malignancy with metastasis to the appendix, incomplete clinicopathologic data, appendicitis as a preoperative diagnosis, primary fallopian tube cancer, primary peritoneal cancer, or documented dual primary tumors. Fifty-seven patients were included in this analysis. The median age was 47 years (range, 13–75). Median follow-up was 53 months (range, 3–147). Histologic diagnoses were as follows: invasive epithelial carcinoma, 35 patients (61%); tumor of low malignant potential, 15 patients (26%); malignant germ cell tumor, 4 patients (7%); and other, 3 patients (5%). Twenty-three patients (40%) had pure mucinous tumors. Forty-six patients (81%) had stage I and 11 patients (19%) had stage II disease. The median CA-125 level was 36.2 U/mL (range, 7–7900). No patient had evidence of appendiceal involvement. No patient suffered an intraoperative or postoperative complication directly related to appendectomy. Appendectomy at the time of surgery for apparent early-stage ovarian cancer is not associated with complications but should not be routinely recommended

Evaluating the psychometric properties of the Immunotherapy module of the MD Anderson Symptom Inventory

Introduction Immunotherapies have revolutionized the treatment of various cancers, but little is known about their symptomatic toxicity. Assessing these symptoms is best accomplished by asking the patients themselves. However, such reports are subjective and may face challenges as bonafide scientific data. Demonstrating the validity of symptom assessment tools, mainly through the reduction of measurement errors, has the potential to improve patient care if these tools are widely adopted. To that end, we present herein the psychometric properties of the Immunotherapy for Early-Phase Trials module of the MD Anderson Symptom Inventory (MDASI-Immunotherapy EPT) in patients receiving various immunotherapies in early phase trials at a major cancer center.Methods One hundred forty-five patients completed the inventory at baseline, with 85 of them also doing so after 9 weeks of treatment. The mean (±SD) age of the patients was 57.0±12.9 years. Also, 56% of the patients were women, 79% identified as white, and 49% had at least some college education.Results The internal consistency reliability of the MDASI-Immunotherapy EPT was excellent, as the Cronbach’s alphas for all of its subscales were at least 0.88 (range 0.88–0.95). Known-group validity based on Eastern Cooperative Oncology Group performance status groupings was excellent at 9 weeks after the start of an immunotherapy trial for the MDASI-Immunotherapy EPT severity (effect size, 0.96) and interference (effect size, 0.82) subscales. We found substantial changes in the symptom items difficulty remembering (effect size, −0.85), fever and/or chills (effect size, −0.63), disturbed sleep (effect size, −0.52), diarrhea (effect size, −0.42), and swelling of hands, legs, or feet (effect size, −0.39).Conclusions In conclusion, the MDASI-Immunotherapy EPT is a valid, reliable, and sensitive tool for measuring symptomatic toxicity