Background
KEYNOTE‐063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second‐line therapy in Asian patients with advanced programmed death ligand 1 (PD‐L1)–positive (combined positive ...score ≥1) gastric/gastroesophageal junction (GEJ) cancer.
Methods
This randomized, open‐label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression‐free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.
Results
Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE‐061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval CI, 4‐10 months) with pembrolizumab versus 8 months (95% CI, 5‐11 months) with paclitaxel (hazard ratio HR, 0.99; 95% CI, 0.63‐1.54). Median PFS was 2 months (95% CI, 1‐3 months) with pembrolizumab versus 4 months (95% CI, 3‐6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04‐2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any‐grade treatment‐related adverse events occurred in 28 pembrolizumab‐treated patients (60%) and 42 paclitaxel‐treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively.
Conclusions
Definitive conclusions about the efficacy of second‐line pembrolizumab in Asian patients with advanced PD‐L1–positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE‐061 trial.
In this small sample of Asian patients with advanced PD‐L1–positive (combined positive score CPS ≥1) gastric/gastroesophageal junction (GEJ) cancer enrolled in the randomized, open‐label, phase 3 KEYNOTE‐063 study, definitive conclusions on clinical outcomes are limited; however, second‐line pembrolizumab monotherapy seems to be well tolerated in this patient population. These findings are consistent with those of the larger global KEYNOTE‐061 study in patients with CPS ≥1 gastric/GEJ cancer.
Aim
Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. ...Omega‐3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega‐3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy.
Methods
A double‐blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP 30 billion colony‐forming unit (CFUs) per sachet at a dose of two sachets daily for 4 weeks, and omega‐3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α) and C‐reactive protein.
Results
The supplementation with MCP and omega‐3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega‐3 fatty acid also managed to reduce the level of IL‐6 (P = 0.002). There was a significant rise in the placebo group's serum TNF‐α (P = 0.048) and IL‐6 (P = 0.004).
Conclusion
The combined supplementation with MCP and omega‐3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy.
Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.
KEYNOTE-048 was a randomised, phase ...3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031.
Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio HR 0·61 95% CI 0·45–0·83, p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 0·64–0·96, p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 0·71–1·03). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 95% CI 0·63–0·93, p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 0·45–0·82, p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 0·53–0·80, p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group.
Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC.
Merck Sharp & Dohme.
Background
A diagnosis of cancer negatively impacts the financial wellbeing of affected individuals as well as their households. We aimed to gain an in‐depth understanding of the financial needs ...following diagnosis of breast cancer in a middle‐income setting with universal health coverage.
Materials and Methods
Twelve focus group discussions (n = 64) were conducted with women with breast cancer from two public and three private hospitals. This study specifically focused on (a) health costs, (b) nonhealth costs, (c) employment and earnings, and (d) financial assistance. Thematic analysis was used.
Results
Financial needs related to cancer treatment and health care varied according to the participant's socioeconomic background and type of medical insurance. Although having medical insurance alleviated cancer treatment‐related financial difficulties, limited policy coverage for cancer care and suboptimal reimbursement policies were common complaints. Nonhealth expenditures were also cited as an important source of financial distress; patients from low‐income households reported transport and parking costs as troublesome, with some struggling to afford basic necessities, whereas participants from higher‐income households mentioned hired help, special food and/or supplements and appliances as expensive needs following cancer. Needy patients had a hard time navigating through the complex system to obtain financial support. Irrespective of socioeconomic status, reductions in household income due to loss of employment and/or earnings were a major source of economic hardship.
Conclusion
There are many unmet financial needs following a diagnosis of (breast) cancer even in settings with universal health coverage. Health care professionals may only be able to fulfill these unmet needs through multisectoral collaborations, catalyzed by strong political will.
Implications for Practice
As unmet financial needs exist among patients with cancer across all socioeconomic groups, including for patients with medical insurance, financial navigation should be prioritized as an important component of cancer survivorship services, including in the low‐ and middle‐income settings. Apart from assisting survivors to understand the costs of cancer care, navigate the complex system to obtain financial assistance, or file health insurance claims, any planned patient navigation program should also provide support to deal with employment‐related challenges and navigate return to work. It is also echoed that costs for essential personal items (e.g., breast prostheses) should be covered by health insurance or subsidized by the government.
Financial concerns related to cancer care are affected by patients' ability to meet the extra expenses, as well as by the legal, health, and social welfare systems in place. This article reports on the financial needs following diagnosis of breast cancer in a middle‐income setting with universal health coverage, focusing on health costs, non‐health costs, employment and earning, and financial assistance.
The incidence of colorectal cancer (CRC) is rapidly rising in several Asian countries, including Malaysia, but there is little data on health care provider costs in this region. The aim of this study ...was to estimate the cost of CRC management from the perspective of the health care provider, based on standard operating procedures.
A combination of top-down approach and activity-based costing was applied. The standard operating procedure (SOP) for CRC was developed for each stage according to national data and guidelines at the University of Malaya Medical Centre (UMMC). The unit cost was calculated and incorporated into the treatment pathway in order to obtain the total cost of managing a single CRC patient according to the stage of illness. The cost data were represented by means and standard deviation and the results were demonstrated by tabulation. All cost data are presented in Malaysian Ringgit (RM). The cost difference between early stage (Stage I) and late stage (Stage II-IV) was analysed using independent
-test.
The cost per patient increased with stage of CRC, from RM13,672 (USD4,410.30) for stage I, to RM27,972 (USD9,023.20) for Stage IV. The early stage had statistically significant lower cost compared to late stage
(2) = -4.729,
= 0.042. The highest fraction of the cost was related to surgery for Stage I, but was superseded by oncology day care treatment for Stages II-IV. CRC is a costly illness. From a provider perspective, the highest cost was found in Stages III and IV. The early stages conserved more resources than did the advanced stages of cancer.
Early diagnosis and management of CRC, therefore, not only affects oncologic prognosis, but has implications for health care costs. This adds further justification to develop and implement CRC screening programmes in Malaysia.
Abstract only
6505
Background: 1L P vs E improved OS in PD-L1 CPS ≥20 and CPS ≥1 populations, and led to noninferior OS in the total population, with favorable safety; 1L P+C vs E had superior OS in ...CPS ≥20, CPS ≥1, and total populations with comparable safety in the phase 3 KEYNOTE-048 study (NCT02358031) in patients with R/M HNSCC. Neither P vs E nor P+C vs E improved PFS in the PD-L1 CPS ≥20, CPS ≥1, or total populations. Here, we present the progression after the next line of therapy (PFS2) to assess the effect of 1L P or P+C and subsequent anticancer therapy on patient outcomes. Methods: Patients with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting were randomly assigned 1:1:1 to P, P+C, or E. PFS2 was defined as time from randomization to objective tumor progression on next-line therapy or death from any cause. PFS2 was estimated using the Kaplan-Meier method as an exploratory outcome confined to those receiving subsequent therapy after 1L P. HR and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate (stratified by ECOG performance status PS, HPV status, and PD-L1 for CPS ≥1 and total populations; by ECOG PS and HPV status for CPS ≥20 population). Data cutoff: Feb 25, 2019. Results: Of 882 (301 P; 281 P+C; 300 E) treated patients,422 (P: 148 49.2%; P+C: 115 40.9%; E: 159 53.0%) received subsequent anticancer therapy after 1L P, most commonly C (P: 135 44.9%; P+C: 88 31.3%; E: 102 34.0%); EGFR inhibitor (P: 59 19.6%; P+C: 37 13.2%; E: 19 6.3%); and immune checkpoint inhibitor (P: 6 2.0%; P+C: 12 4.3%; E: 50 16.7%); patients may have received more than one type of subsequent therapy. Median PFS2 is reported in Table. Conclusions: In patients with R/M HNSCC, longer median PFS2 was observed in the CPS ≥20 and CPS ≥1 populations for P vs E, and in the CPS ≥20, CPS ≥1, and total populations for P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . Table: see text
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