Efficacy of second-line chemotherapy or immune checkpoint inhibitors for patients with a prolonged objective response (≥ 6 months) after first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma: a retrospective study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose. METHODS: Retrospective analysis (six French centers, 2008-2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. PRIMARY ENDPOINT: progression-free survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy. RESULTS: R/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line. Response after first-line: complete response (CR; n = 16, 11%); partial response (PR; n = 77, 53%); stable disease (n = 22, 15%). Second-line therapy: PBC (n = 95, 66%); platinum-free regimen (PFR) (n = 25, 17%); ICI (n = 24, 17%). Median [95% confidence interval] PFS (months): PBC 5.0 [3.8-6.2]; PFR 4.0 [1-7.0]; ICI 2.0 [0.4-3.6] (p = 0.16). For PBC, PFR, and ICI, respectively: OS1 30, 23, and 29 months (p = 1.02); OS2 14, 10, and 16 months (p = 0.25); PR, 26%, 16%, and 21% patients; CR, 0%, 8%, and 4% patients. For subsequent lines, ICIs were administered for PBC (n = 11, 12%) and PFR (n = 2, 8%). No predictive factor for efficacy (PFS, OS) was identified. CONCLUSIONS: Our retrospective study suggests similar efficacy regarding OS2 for second-line chemotherapy or ICI in R/M-HNSCC patients with progression ≥ 6 months after the last first-line platinum dose.

Clinical Impact of High Throughput Sequencing on Liquid Biopsy in Advanced Solid Cancer.

BACKGROUND: Cancer therapies targeting actionable molecular alterations (AMA) have developed, but the clinical routine impact of high-throughput molecular profiling remains unclear. We present a monocentric experience of molecular profiling based on liquid biopsy in patients with cancer. METHODS: Patients included had solid cancer and underwent cfDNA genomic profiling with FoudationOne Liquid CDx (F1LCDx) test, analyzing 324 genes. Primary endpoint was to describe patients with an AMA for whom clinical decisions were impacted by F1LCDx test results. RESULTS: 191 patients were included, mostly with lung cancer (46%). An AMA was found in 52%. The most common molecular alterations were: TP53 (52%), KRAS (14%) and DNMT3 (11%). The most common AMA were: CHEK2 (10%), PIK3CA (9%), ATM (7%). There was no difference in progression-free survival (2.66 months vs. 3.81 months, p = 0.17), overall survival (5.3 months vs. 7.1 months, p = 0.64), or PFS2/PFS1 ratio ≥ 1.3 (20% vs. 24%, p = 0.72) between patients receiving a molecularly matched therapy (MMT) or a non-MMT, respectively. Patients with a MMT had an overall response rate of 19% and a disease control of 32%. CONCLUSIONS: Routine cfDNA molecular profiling is feasible and can lead to the access of targeted therapies. However, no notable benefit in patient's outcomes was shown in this unselected pan-cancer study.

Starting Imatinib at 400 mg Daily in Patients with Gastrointestinal Stromal Tumors Harboring KIT Exon 9 Mutations: A Retrospective, Multicenter Study.

BACKGROUND: Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled. OBJECTIVE: We aimed to retrospectively assess the activity of imatinib 400 mg in both the adjuvant and the advanced settings. PATIENTS AND METHODS: We performed a multicenter study of patients with KIT exon 9-mutated GIST starting imatinib at 400 mg daily. We examined the relapse-free survival (RFS) among high-risk patients either receiving or not receiving adjuvant imatinib. In patients with advanced disease, progression-free survival (PFS, progression under imatinib 400 mg), time to imatinib failure (TIF, progression under imatinib 400, then 800 mg upon first progression), and overall survival (OS) were analyzed. RESULTS: In the post-operative setting (n = 37), 20 patients received adjuvant imatinib. Median RFS in high-risk patients receiving adjuvant imatinib (n = 14) was not reached (95% CI 17.5-46.6) versus 13.6 months (95% CI 4.7-13.6) for those who did not (p = 0.37), after a median follow-up of 58 months. RFS at 36 months was 63% (30.3-96.6) versus 40% (95% CI 0-82.9), p = 0.2. In advanced disease (n = 28), median PFS, TIF and OS were 12.7 months (95% CI 6.1-18.2), 21.0 months (95% CI 17.4-28.1) and 47.0 months (95% CI 33.5-69.2), respectively. CONCLUSIONS: Despite the limitations of a retrospective analysis and the small number of patients, the benefit of adjuvant imatinib 400 mg daily in high-risk patients appeared relevant. Patients with advanced disease receiving imatinib 400 mg with subsequent dose escalation had a TIF similar to that observed with an initial dose of 800 mg. Intra-patient dose escalation in this setting might be an option.

Cetuximab combined with paclitaxel or paclitaxel alone for patients with recurrent or metastatic head and neck squamous cell carcinoma progressing after EXTREME.

BACKGROUND: Prognosis of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) remains poor. The addition of cetuximab, to platinum and fluorouracil chemotherapy (EXTREME regimen) has been shown to improve patients' outcomes in first-line settings. METHODS: We conducted a retrospective, multicenter study, including HNSCC that progressed after a first line of platinum-based chemotherapy and cetuximab, treated either by paclitaxel + cetuximab (PC) or paclitaxel alone (P), between January 2010 and April 2018. The end points were overall survival (OS), progression-free survival (PFS), and overall response rates (ORR). Patients were matched according to their propensity scores, estimated with a logistic regression model. The secondary objectives were to study the safety profile and to look for prognostic and predictive factors of effectiveness. RESULTS: Of the 340 identified patients, 262 were included in the analysis, 165 received PC, and 97 received P. In unmatched population, ORR was 16.4% with PC and 6.2% for P. Median PFS was 2.9 months [95% Confidence Interval 2.7-3.0] for PC versus 2.5 months [2.2-2.7] for P, hazard ratio (HR) = 0.770 [0.596-0.996]. Median OS was 5.5 months [4.4-6.9] for PC versus 4.2 months [3.4-4.8] for P, HR = 0.774 [0.590-1.015]. In multivariate analysis, PC was associated with better PFS and OS. These results were consistent in matched-paired population. Previous cetuximab maintenance for more than 3 months was predictive of better OS with PC. CONCLUSION: Although the continuation of cetuximab in combination with paclitaxel after EXTREME provides moderate benefit, it could be an interesting option for selected patients.

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients.

BACKGROUND: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. METHOD: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. RESULTS: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26-0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. CONCLUSION: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.

Persistence with biological drugs in patients treated in rheumatology practices in Germany.

The goal of this study was to investigate the persistence with biological drugs in patients treated in rheumatology practices in Germany. This study included patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PA), or ankylosing spondylitis (AS) who received a first prescription of biological drugs between 2008 and 2016 (index date) in 21 rheumatology practices in Germany (n = 4925; Disease Analyzer database). The main outcome measure was the rate of persistence within 5 years of the index date. Kaplan-Meier analyses were performed to study treatment persistence as a function of diagnosis, gender and age. A Cox proportional hazards regression model was used to estimate the relationship between non-persistence and diagnosis, gender, age, and comorbidities. After 5 years of follow-up, the rate of persistence was 31.8% in patients with RA, 35.2% in those with AS, and 33.2% in those with PA (log-rank p value = 0.028). Furthermore, 33.8% of men and 31.9% of women were persistent (log-rank p value = 0.035). The rate of persistence was 20.8%, 27.9%, 33.0%, 36.6%, 35.2%, and 32.0% in people aged ≤ 30, 31-40, 41-50, 51-60, 61-70, and > 70 years, respectively (log-rank p value = 0.002). The risk of discontinuation was lower in participants diagnosed with AS than in those diagnosed with RA [hazard ratio (HR) = 0.87; 95% confidence interval (CI) 0.79-0.96]. In addition, patients aged ≤ 30 years were more likely to discontinue their biological therapy than those aged > 70 years (HR = 1.29; 95% CI 1.10-1.52). Persistence with biological drugs was low after 5 years of follow-up in rheumatology practices.

Building and Validating a Computerized Algorithm for Surveillance of Ventilator-Associated Events.

OBJECTIVE: To develop an automated method for ventilator-associated condition (VAC) surveillance and to compare its accuracy and efficiency with manual VAC surveillance SETTING: The intensive care units (ICUs) of 4 hospitals METHODS: This study was conducted at Detroit Medical Center, a tertiary care center in metropolitan Detroit. A total of 128 ICU beds in 4 acute care hospitals were included during the study period from August to October 2013. The automated VAC algorithm was implemented and utilized for 1 month by all study hospitals. Simultaneous manual VAC surveillance was conducted by 2 infection preventionists and 1 infection control fellow who were blinded to each another's findings and to the automated VAC algorithm results. The VACs identified by the 2 surveillance processes were compared. RESULTS: During the study period, 110 patients from all the included hospitals were mechanically ventilated and were evaluated for VAC for a total of 992 mechanical ventilation days. The automated VAC algorithm identified 39 VACs with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%. In comparison, the combined efforts of the IPs and the infection control fellow detected 58.9% of VACs, with 59% sensitivity, 99% specificity, 91% PPV, and 92% NPV. Moreover, the automated VAC algorithm was extremely efficient, requiring only 1 minute to detect VACs over a 1-month period, compared to 60.7 minutes using manual surveillance. CONCLUSIONS: The automated VAC algorithm is efficient and accurate and is ready to be used routinely for VAC surveillance. Furthermore, its implementation can optimize the sensitivity and specificity of VAC identification.

Observer bias in hand hygiene compliance reporting.

Differences in reported hand hygiene compliance rates were assessed on the basis of the unit affiliation of observers. In 2 hospitals, unit-based observers more often reported higher compliance rates than did non-unit-based observers (79% vs 58.6%; difference, 20.4%; P<.001). Nonstandardized data collection methods contribute to the variability in hand hygiene compliance rates.