Italian results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer.

The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0-1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.

Lay abstract PRECONNECT is an international study demonstrating the efficacy and tolerability of the drug combination trifluridine/tipiracil in adult patients with metastatic colorectal cancer treated in everyday clinical practice. For this publication, the authors conducted an analysis performed on the 161 Italian patients enrolled in this study. These kinds of analyses are important because of the differences that may arise across different countries. The most common contraindications were not dangerous to health. Furthermore, 3 months from beginning the medication, half of the patients did not show a worsening of the disease and quality of life during treatment was maintained. Clinical trial registration: NCT03306394 (ClinicalTrials.gov).

Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.

BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. RESULTS: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075). CONCLUSIONS: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.

Using peripheral immune-inflammatory blood markers in tumors treated with immune checkpoint inhibitors: An INVIDIa-2 study sub-analysis.

The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of <3.4 (p < 0.001) and <831 (p < 0.001) were independent factors for OS in multivariate analysis. SII with LR, ROC, or CV significantly predicted OS in NSCLC (p = 0.002, p = 0.003, p = 0.003), RCC (p = 0.034, p = 0.014, p = 0.014), and melanoma (p = 0.038, p = 0.022, p = 0.019). NLR with LR and ROC cutoffs predicted OS in first line (p < 0.001 for both) and second line or beyond (p = 0.006 for both); likewise SII (p < 0.001; p = 0.002 and p < 0.001). NLR and SII are prognosticators in NSCLC, RCC, and melanoma treated with ICIs.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: report of a case and review of the literature with demonstration of genes alteration into the same tumor cells.

Oncogenic drivers in lung non-small-cell lung cancer (NSCLC) are considered mutually exclusive, but a review of the literature reveals that concomitant EGFR mutations and ALK rearrangement may occur in a subset of NSCLC. We report here a case of pulmonary adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in naive and relapsed tumors. Tumor cells seem to harbor both gene alterations and the patient had a long-lasting response both to EGFR inhibitor in second line and ALK inhibitor once tumor progressed. A speculative discussion on molecular mechanisms underlying this uncommon phenomenon and practical points about epidemiologic, clinicopathologic features and therapeutic options in this intriguing subset of double-positive tumor are reported.