Sing Hung Lo

PURPOSE Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR -mutant, metastatic non–small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837 ). METHODS Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS. RESULTS Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients. CONCLUSION Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.

BACKGROUND: Ketamine has been used as an adjuvant to opioid therapy for the management of refractory cancer pain but the current evidence is insufficient to draw any conclusions regarding its efficacy. We aimed to assess the response to ketamine in patients with refractory cancer pain treated in an oncology palliative care unit. METHODS: Patients with refractory cancer pain despite opioid dose escalation were selected for a trial of parenteral ketamine infusion according to a local protocol. The medical records of those patients treated between January 2004 and December 2018 were retrospectively reviewed. The primary endpoint of the study was a favorable response to ketamine, defined as a reduction in regular opioid dose with no increase in pain intensity or a reduction in pain intensity by ≥2 points on the numerical rating scale (NRS) with a stable regular opioid dose. The secondary endpoint was adverse events associated with ketamine. RESULTS: Among the 70 patients, mean pain score on NRS improved from 7.0 to 4.0 after ketamine (P<0.001). Forty-nine patients had a reduction of pain score by ≥2 points on NRS, 33 had ≥50% reduction in pain intensity. The median decrease in regular opioid dose was 25.5%, and the mean difference was -133.2 mg (P=0.002). A favorable response to ketamine was observed in 52 patients (74.3%). The use of more than one coanalgesic (odds ratio 3.451; 95% CI: 1.087-10.960; P=0.036) was associated with a favorable response to ketamine on multivariate analysis. Adverse events were mostly mild, with the commonest being drowsiness (45.7%), hypertension (34.3%) and nightmares (25.7%). Only five and three patients required temporary suspension and early termination of ketamine infusion respectively. CONCLUSIONS: These data demonstrated the efficacy and safety of ketamine in a population of patients with refractory cancer pain. The use of more than one coanalgesic was associated with a favorable response to ketamine. Further large and multicentered studies are warranted to confirm these data.

BACKGROUND: Indwelling abdominal drains for intermittent drainage is an effective treatment for refractory malignant ascites, bacterial colonization and subsequent drain-related infection is however a common concern. This study aimed to investigate the patterns of bacterial colonization and the subsequent infection outcomes in patients with indwelling abdominal drains. METHODS: All consecutive advanced cancer patients with newly inserted indwelling abdominal drains and who were under the service of the ascites clinic of our institution for intermittent drainage between January 2011 and March 2018 were screened for study eligibility. Patients with positive surveillance ascitic fluid culture without immediate drain-related infection were included in the final analysis. Clinical information during the drainage period was prospectively collected using standardized clinical assessment forms. These assessment forms and other medical records were retrospectively reviewed. RESULTS: Sixty nine patients developed bacterial colonization without immediate infection during the study period. The most common cancer diagnosis was hepatocellular carcinoma (HCC), which comprise 30.4% of the population. Central venous catheters (CVCs) were inserted in 76.8% of patients and pigtail drains in 23.2% as the indwelling abdominal drain. The median duration from drain insertion to the development of bacterial colonization was 18.0 days. Staphylococci, Diphtheroid bacilliand Enterococci were the most common types of bacteria isolated during colonization. Thirty patients (43.5%) developed drain-related infection subsequently and the median time from bacterial colonization to development of infection was 14.5 days. The incidence rate of drain-related infection after bacterial colonization was 1.78 per 100-catheter days and the 1-month infection-free survival was 54.4%. Five patients (7.2%) developed peritonitis and 4 of them died from the infection episode. Decrease in body mass index (BMI) (P=0.03), having 3 or more episodes of drainage in the ascites clinic before bacterial colonization (P=0.03), presence of Escherichia coli (P=0.04) and Bacillus species (P=0.04) in surveillance ascitic fluid culture were significantly correlating with infection outcomes in univariate analyses. HCC as cancer diagnosis (OR 8.85, 95% CI: 1.86-42.07, P=0.006) and decrease in body weight (OR 1.20, 95% CI: 1.02-1.42, P=0.03) were significant factors that correlated with infection outcomes in multivariate analysis. CONCLUSIONS: Bacterial colonization and subsequent progression into drain-related infection are common in patients on indwelling abdominal drains for malignant ascites. Staphylococci is the most common type of bacteria causing both colonization and subsequent drain-related infection. HCC and decrease in body weight are significant factors that correlate with infection outcomes after bacterial colonization.