Antibiotics impair immune checkpoint inhibitor effectiveness in Hispanic patients with non-small cell lung cancer (AB-CLICaP).

BACKGROUND: The intestinal microbiota is an important factor in modulating immune-mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments. METHODS: This was a retrospective cohort study. Patients with advanced non-small cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 (PD-L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non-ATB exposed (no-ATB), exposed within 30 days of the first dose of ICI (pre-ICI ATB) and patients receiving ATB concomitantly with ICI (ICI-ATB). Progression-free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed. RESULTS: A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B-lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32-67.7), compared with 20.3 months (95% CI: 12.1-non-reached [NR]) for patients with pre-ICI ATB treatment and 24.7 months (95% CI: 13-NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups. CONCLUSIONS: Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs.

Atypical Skin Manifestations During Immune Checkpoint Blockage in Coronavirus Disease 2019-Infected Patients With Lung Cancer.

A new coronavirus, named severe acute respiratory syndrome-coronavirus-2 by the WHO, has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, the People's Republic of China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100,000 deaths. With approximately 20 million new cases globally per year, cancer affects a substantial portion of the population. Individuals affected by cancer are more susceptible to infections owing to coexisting chronic diseases (cardiovascular, pulmonary, and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and the anticancer treatment. As a consequence, patients with malignancies, especially those with lung cancer who develop coronavirus disease 2019, experience more difficult outcomes. A recent multicenter study carried out by the Hubei Anti-Cancer Association has also documented that patients with lung cancer had an increased risk of death, intensive care unit requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here, we present two representative cases of patients with lung cancer and coronavirus disease 2019 without respiratory compromise and with atypical and severe skin manifestations-findings that could be influenced by the long-term use of anti-programmed cell death protein 1 antibody.

Mortality and Advanced Support Requirement for Patients With Cancer With COVID-19: A Mathematical Dynamic Model for Latin America.

PURPOSE: In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis. METHODS: We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model. RESULTS: Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between < 1% to 17.6% of all patients with cancer in the region. CONCLUSION: Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer.

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non-small cell lung cancer (NSCLC) compared with chemotherapy (Quijote-CLICaP).

BACKGROUND: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second- or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. METHODS: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third- or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. RESULTS: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%, [95% CI 14.5-25.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. CONCLUSIONS: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

EGFR exon 20 insertion in lung adenocarcinomas among Hispanics (geno1.2-CLICaP).

OBJECTIVES: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients. MATERIALS AND METHODS: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach. RESULTS AND CONCLUSIONS: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm.

Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP).

BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. RESULTS: Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). CONCLUSIONS: Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.

C-reactive protein and the MASCC risk index identify high-risk patients with febrile neutropenia and hematologic neoplasms.

OBJECTIVE: The objective of this study is to assess the prognostic usefulness of the Multinational Association of Supportive Care in Cancer (MASCC) risk score in association with the value of C-reactive protein (CRP) to identify high-risk patients with febrile neutropenia and hematologic neoplasms. METHODS: A retrospective cohort study in which the MASCC score and the CRP values were used to assess the mortality risk at 30 days among patients with febrile neutropenia and hematologic malignancies was performed. RESULTS: Two hundred thiry-seven patients with febrile neutropenia were analyzed; the mortality rate within 30 days was 9 %. High-risk patients according to the MASCC score were significantly more likely to experience adverse outcomes, such as being transferred to the intensive care unit (RR 3.55; CI 95 % 2.73-6.62, p < 0.001) and death (RR 2.21; CI 95 % 1.74-2.79, p < 0.001). Multivariate analysis showed a strong association between the high-risk group identified by the MASCC score (HR 3.0; CI 95 % 1.12-13.54, p = 0.032) and the mean levels of CRP (HR 17; CI 95 % 2.21-136.48, p = 0.007) and survival. The survival rate within 30 days was 100 % for the patients with a low-risk MASCC score and a mean CRP less than 15 mg/dL. This rate was only 64 % for high-risk patients with a mean CRP greater than 15 mg/dL. CONCLUSION: The MASCC risk score combined with the mean CRP value successfully identifies patients with febrile neutropenia and hematological malignancies and a high risk of death.