Chemotherapy-induced nausea and vomiting (CINV) in patients with advanced lung cancer during the first-line treatment: assessment by physicians, nurses, and patients from an Italian multicenter survey.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses. METHODS: This observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen's kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development. RESULTS: The incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively. CONCLUSIONS: Despite clinical staff awareness of patients' status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development.

Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

FHIT and p53 status and response to platinum-based treatment in advanced non-small cell lung cancer.

Inactivation of the FHIT and TP53 genes is frequently observed in primary non-small cell lung cancers (NSCLC) and cell lines and may contribute to resistance to apoptotic stimuli elicited by various anti-tumor drugs. To evaluate a possible relationship between FHIT and TP53 status and response to platinum-analogue regimens, we retrospectively selected 55 NSCLC patients treated with carboplatin/gemcitabine. Pre-treatment formalin fixed biopsies were analyzed for FHIT and p53 protein expression by immunohistochemistry and representative micro dissected tissue for TP53 mutations by DG-DGGE/sequencing. The FHIT-negative immunophenotype (FHIT-, pathologic) was found in 33 patients (60%) and p53 over expression/mutation (p53+, pathologic) in 25 patients (45%). The FHIT-/p53+ combination was present in 12 patients (22%). Overall, there was partial response in 21 patients (38%), with subgroup response rates of 33% in FHIT+/p53-, 46% in FHIT+/p53+, 38% in FHIT-/p53- and 33% in FHIT-/p53+ patients. Median progression-free survival (PFS) was 9.6, 7.9, 6.8 and 5.9 months and median overall survival (OS) was 12.8, 11.9, 10.5 and 8.7 months in the four groups, respectively. The Group comparison showed significantly worse PFS (p=0.04) in FHIT-/p53+ than the other groups. There was no significant difference in OS between the groups. A trend (p=0.07) for shorter OS was found in FHIT- cases suggesting that NSCLC tumors carrying this feature are less responsive to treatment. This retrospective study indicates that FHIT-/p53+ status might be a biological variable influencing the efficacy of carboplatin/gemcitabine treatment in NSCLC.