Safety of Combination Immune Checkpoint Inhibitors Compared to Monotherapy; A Systematic Review and Meta-Analysis.

Combination immune checkpoint inhibitors (ICIs) achieved higher efficacy than monotherapy in many types of cancers. We searched PubMed, Scopus, and Cochrane databases for randomized phase II/III trials in cancer patients receiving combination ICIs vs. Monotherapy. Our search retrieved 934 records. Eight studies were found to be eligible for meta-analysis recruiting 2544 patients. Combined immunotherapy nivolumab plus ipilimumab was associated with statistically significant higher risk of all grade adverse events (AE), and discontinuation due to all grade AEs as compared to both ipilimumab or nivolumab. Although combination ICIs showed better oncological activity, it carried a higher risk of all grade irAEs.

Reliability and validity of the Arabic translation of the palliative performance scale.

OBJECTIVE: The aim of this study was to translate the Palliative Performance Scale (PPSv2) into Arabic and to test the reliability and validity of the PPS Arabic translation (PPS-Arabic). METHOD: The PPSv2 was translated into Modern Standard Arabic using a forward-backward method. Inter-rater and intra-rater reliabilities were tested in a pilot study that included 20 patients. The validation study included 150 cancer patients. Patients were divided according to their treatment plan into three groups (in-remission, palliative chemotherapy, and best supportive care) to perform hypothesis-testing construct validity. Validity was further evaluated by correlating PPS-Arabic with the Karnofsky Performance Scale (KPS), the Eastern Cooperative Oncology Group (ECOG) scale, and Physical Functioning (PF2) and Role Functioning (RF2) scales of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). RESULTS: The intraclass correlation coefficients for the intra-rater and inter-rater reliability were 0.935 (95% CI: 0.88-0.965; p < 0.001) and 0.965 (95% CI: 0.934-0.981; p < 0.001), respectively. The PPS-Arabic internal consistency Cronbach's alpha was 0.986. The average PPS-Arabic score differed significantly (p < 0.001) between the three groups of patients being 89 for in-remission, 58 for palliative chemotherapy, and 38 for best supportive care. The PPS-Arabic score correlated significantly (p < 0.001) with the KPS, ECOG performance scale, and the EORTC QLQ-C30 PF2 and RF2 scales. CONCLUSION: The PPS-Arabic is a reliable and valid tool for the assessment of performance status of cancer patients.

Combination of metronomic capecitabine and letrozole in metastatic hormone receptor positive, HER2 negative breast cancer: a randomized phase II trial.

First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m2 BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (p = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.