Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer.

A dose of 200 mg 3-weekly of pembrolizumab was approved by the Food and Drug Administration (FDA) as treatment for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2 mg/kg. Our study aimed to assess the efficacy of a lower fixed dose of 100 mg, which is closer to 2 mg/kg weight-based dose in an average-sized Asian patient. All patients receiving pembrolizumab for advanced NSCLC from January 2016 to March 2020 in National University Hospital, Singapore, were included in this retrospective observational study. The effect of pembrolizumab 100 mg (Pem100) vs 200 mg (Pem200) upon survival outcomes, toxicity and cost were examined. One hundred fourteen patients received pembrolizumab. Sixty-five (57%) and 49 (43%) received Pem100 and Pem200, respectively. There was no difference in progression-free survival (PFS) and overall survival (OS) between Pem100 vs Pem200 as a single agent (PFS: 6.8 vs 4.2 months, hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.36-1.46, P = .36; 9 month OS: 58% vs 63%, HR 1.08, 95% CI 0.48-2.41, P = .86) and when combined with chemotherapy (9-month PFS: 60% vs 50%, HR0.84, 95% CI 0.34-2.08, P = .71; 9-month OS: 85% vs 58%, HR 0.27, 95% CI 0.062-1.20, P = .09). No significant difference in response rate or ≥G3 immune-related toxicities between Pem100 and Pem200 was observed. A cost minimisation analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of SGD4,290,912 and cost saving per patient of SGD39,942 in the Pem100 group. A 100 mg of pembrolizumab appears to be effective with reduction in cost. A randomised trial should be done to investigate a lower dose of pembrolizumab.

Reducing Chemotherapy Waiting Times in the Ambulatory Setting of a Tertiary Cancer Centre Using a Design Thinking Approach.

INTRODUCTION: Chemotherapy is complex. We hypothesized that a design thinking approach could redesign preparatory processes and reduce wait times. METHODS: A multidisciplinary process mapping exercise was undertaken to understand the current processes, followed by proposing and testing solutions. Proposals were selected based on desirability and feasibility. These focused on starting the morning treatments on time and scheduling pre-made regimens in these slots. The primary outcome measure was the time from the appointment to starting treatment. Treatments in the post-intervention study group were compared against a historical control group. RESULTS: The median time to start morning treatment decreased by 46%, from 83 min (with an interquartile range 50-127) in the control group to 45 min (with an interquartile range of 24-81 min) in the study group (p < 0.001). This translated into an overall improvement for the day, with the median time to start treatment decreasing from 77 min (with an interquartile range of 40-120 min) to 47 min (with an interquartile range of 20-79 min) (p < 0.001). Pre-makes increased by 258%, from 908 (28.5%) to 2340 (71.7%) regimens (p < 0.001). The number of patients starting treatment within an hour of their appointment increased from 1688 (32.8%) to 3355 (62.3%, p < 0.001). CONCLUSION: We have shown that a data-driven, design thinking approach can improve waiting times. This can be adapted to improve other processes in an empathetic, sustainable manner.

Real-world assessment of attenuated dosing anti-PD1 therapy as an alternative dosing strategy in a high-income country (as defined by World Bank).

The rising cost of oncological drugs poses a global challenge to patients, insurers, and policy makers, with the leading drugs worldwide by revenue from immune checkpoint inhibitors (ICIs). Despite its cost, ICI is marked as a paradigm shift, offering the potential of a long-term cure. To reduce cost, an attenuated dose of ICI based on pharmacological principles can be used while maintaining efficacy. This real-world study aims to examine the prescribing patterns, the effect of financial constraints, and the outcomes in non-small cell lung cancer (NSCLC). All patients receiving palliative intent ICI treatment for advanced NSCLC between January 2014 and April 2021 in National University Hospital, Singapore were recruited. Demographics, prescription trends, factors affecting the prescription of attenuated dose ICI (AD ICI) versus standard dose ICI (SD ICI), and the effect of dose on survival outcomes, toxicities, and costs were examined. Two hundred seventy-four received ICI. The majority of them were treated in first-line setting. One hundred sixty-two (59%) of patients received AD ICI, whereas 112 (41%) received SD ICI. Patients who did not have a supplemental private as-charged health insurance plan were more likely to have received AD ICI (OR: 4.53 [2.69-7.61] p < 0.001). There was no difference in progression-free survival (PFS) and overall survival (OS)-adjusted HR 1.07 CI [0.76, 1.50] p = 0.697 and HR 0.95 CI [0.67, 1.34] p = 0.773, respectively, between patients who received AD versus SD ICI. A cost minimization analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of USD 7,939,059 over 7 years. Our study provides evidence for AD-ICI as a promising strategy to maximize the number of patients who can be treated with ICI. This has the potential to make significant economic impact and allow more patients to benefit from novel therapies.

Immune checkpoint inhibition for non-small cell lung cancer in patients with pulmonary tuberculosis or Hepatitis B: Experience from a single Asian centre.

BACKGROUND: The importance of immune-checkpoint inhibitors (ICI) can no longer be understated since its move to front-line treatment in non-small cell lung cancer (NSCLC) in recent years. However, the safety and efficacy of ICI in special populations such as those with infections like tuberculosis (TB) and hepatitis B (HBV) remain unknown as they are routinely excluded from clinical trials. METHODS: Records of patients with advanced NSCLC who were treated with ICI from January 2014 to June 2019 at a single Asian centre were reviewed. Those with a history of HBV and/or TB were selected. In this group, safety and treatment outcomes including overall survival (OS), progression-free survival (PFS) and response rate were reported and compared against control. RESULTS: 191 patients received ICI, 47 (24.6%) had a history of TB/HBV. The median PFS in those with a history of TB/HBV was 5.7 months (95% CI 3.9-7.6), compared to 3.1 months (95% CI 2.4-3.8) in control (HR 0.61, 95% CI 0.39-0.93, p = 0.021). Median OS was 15.6 months (95% CI 10.2-21.0) compared to 11.1 months (95% CI 7.6-14.7 months) in the control group (HR 0.58, 95% CI 0.34-0.99, p = 0.046). Adverse events of any grade (G) were similar in both groups; slightly more patients with TB/HBV experienced G3 or higher adverse events. Four patients developed TB after initiation of ICI, none with previously documented TB experienced reactivation. Of the 42 patients with a history of HBV, eight had inactive chronic HBV and six had detectable viral load. None of the 34 patients who were previously exposed to HBV had reactivation. CONCLUSION: The use of ICI appears to be safe and efficacious in patients with TB/HBV infection. Prospective studies are required to identify those at risk in order to optimise care to these groups of patients.