Platinum-Based Chemotherapy in Older Patients with Non-Small Cell Lung Cancer: What to Expect in the Real World.

BACKGROUND: The role of platinum-based chemotherapy (PBC) for the treatment of older patients with non-small cell lung cancer (NSCLC) is still a matter of debate, despite the advent of immunotherapy. OBJECTIVE: The aim of the study was to identify factors associated with first-line PBC prescription and, secondly, to evaluate the impact of first-line PBC on survival, treatment intensity, risk of hospitalization, and subsequent treatments. PATIENTS AND METHODS: We reviewed a consecutive series of 474 older patients (age ≥ 70 years) diagnosed with stage IIIB-IV NSCLC at the Department of Oncology, University Hospital of Udine, Italy from January 2009 to March 2017. RESULTS: Overall, 198 patients were deemed eligible, and 65.2% received a PBC. At multivariate analysis, older age was the only factor associated with PBC prescription. In the whole cohort, 46 patients (23.2%) were hospitalized for chemotherapy-related toxicity. Both PBC prescription (odds ratio [OR] 2.23, 95% confidence interval [CI] 1.02-4.87, p = 0.04) and tumor burden (OR 2.39, 95% CI 1.07-5.32, p = 0.03) emerged as independent risk factors for hospitalization. Moving to significant predictors of patterns of care, Eastern Cooperative Oncology Group (ECOG) performance status > 0 was associated with greater risk of first-line failure (OR 2.20, 95% CI 1.15-4.20, p = 0.02), while bone metastases (OR 0.29, 95% CI 0.12-0.69, p = 0.005) and a Charlson Comorbidity Index score ≥ 3 (OR 0.40, 95% CI 0.19-0.84, p = 0.016) independently predicted lower probability of receiving second-line therapy. Remarkably, PBC did not significantly impact overall survival (hazard ratio [HR] 0.83, 95% CI 0.61-1.14, p = 0.24) and progression-free survival (HR 0.95, 95% CI 0.70-1.28, p = 0.73) compared to single-agent chemotherapy (SAC). However, according to an exploratory landmark analysis, patients who received four cycles of treatment or maintenance therapy experienced prolonged overall survival, regardless of PBC use. CONCLUSIONS: This study evaluated the real-world use of PBC in older patients with NSCLC, offering an insight into the determinants of its prescription and the pattern of care of these patients. Of note, PBC use was associated with a higher likelihood of hospitalization for chemotherapy-related toxicity, with no benefit on survival compared to SAC.

Bone metastases from head and neck malignancies: Prognostic factors and skeletal-related events.

BACKGROUND: We conducted a multicenter retrospective analysis to describe the characteristics, frequency of skeletal-related events (SREs), and prognosis of head and neck cancer (HNC) in patients with bone metastases (BM). PATIENTS AND METHODS: The data of 192 HNC patients with BMs were collected. Analyses were conducted separately in 64 nasopharyngeal cancer (NPC) patients and in 128 non-NPC patients. RESULTS: SREs occurred in 34 (27%) non-NPC and in 6 (9%) NPC patients, respectively. Median overall survival (OS) was 25 and 6 months in NPC and non-NPC patients, respectively. Locoregional recurrence (hazard ratio [HR] 2.33, 95% confidence interval (CI) 1.1-4.93), synchronous BM (HR 0.25, 95% CI 0.59-0.71) and bone-directed therapies (BDT) (HR 0.26, 95% CI 0.10-0.68) were independent prognostic factors for OS in NPC patients. Combined bone radiotherapy (RT) and BDT in NPC patients obtained longer survival (38 months) than either therapy alone (25 months) or neither of these therapies (8 months). CONCLUSIONS: Patients with BMs from non-NPC have a poor prognosis and are at high risk of SREs. NPC patients with BMs are at relatively low risk of SREs. BDT may potentially improve survival, particularly when combined with bone RT. This last finding deserves prospective confirmation.

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019).

INTRODUCTION: To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC). METHODS: This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m(2) on day 1) with oxaliplatin (70 mg/m(2) on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m(2) on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival. RESULTS: Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively. CONCLUSIONS: The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.

Prognostic stratification of stage IIIA pN2 non-small cell lung cancer by hierarchical clustering analysis of tissue microarray immunostaining data: an Alpe Adria Thoracic Oncology Multidisciplinary Group study (ATOM 014).

INTRODUCTION: Stage IIIA non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node metastases (N2) is a heterogeneous disease with differing prognoses. In this study, we retrospectively investigated the prognostic value of the expression of 10 molecular markers in 87 patients with stage IIIA pN2 NSCLC treated with radical surgery. METHODS: Primary tumor tissue microarrays (TMAs) were constructed and sections used for immunohistochemical analysis of epidermal growth factor receptor, ErbB-2, c-kit, cyclooxygenase-2, survivin, bcl-2, cyclin D1, cyclin B1, metalloproteinase (MMP)-2, and MMP-9. Univariate and multivariate analyses and unsupervised hierarchical clustering analysis of clinical pathologic and immunostaining data were performed. RESULTS: Bcl-2 (p < 0.0001) and cyclin D1 (p = 0.015) were more highly expressed in squamous cell carcinoma (SCC), whereas MMP-2 (p = 0.009), MMP-9 (p = 0.005), and survivin (p = 0.032) had increased expression in other histologic subtypes. In univariate analysis, SCC histology and cyclin D1 expressions were favorable prognostic factors (p = 0.015 and p < 0.0001, respectively); by contrast, MMP-9 expression was associated with worse prognosis (p = 0.042). In multivariate analysis, cyclin D1 was the only positive prognostic factor (p < 0.0001). Unsupervised hierarchical clustering analysis of TMA immunostaining data identified five distinct clusters. They formed two subsets of patients with better (clusters 1 and 2) and worse (clusters 3, 4, and 5) prognoses, and median survival of 51 and 10 months, respectively (p < 0.0001). The better prognosis subset mainly comprised patients with SCC (80%). CONCLUSIONS: Hierarchical clustering of TMA immunostaining data using a limited set of markers identifies patients with stage IIIA pN2 NSCLC at high risk of recurrence, who may benefit from more aggressive treatment.

Phase II study of irinotecan and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 007).

This study was designed to evaluate the activity and tolerability of irinotecan and docetaxel in patients with previously treated non-small cell lung cancer (NSCLC). Eligibility included recurrent or progressive NSCLC, previous chemotherapy, age > or = 18 years, ECOG PS < or = 2. Treatment consisted of irinotecan (160 mg/m2 i.v.), followed by docetaxel (65 mg/m2 i.v.) on day 1 of a 21-day cycle, for a maximum of 6 cycles. Forty patients were enrolled. Median age was 60 years and median ECOG PS was 1. All patients were evaluable for toxicity and 31 (78%) were evaluable for response. A total of 125 cycles was administered (median, 3; range, 1-6). Most common grade 3-4 toxicities were neutropenia (62%), neutropenic fever (22%), and diarrhea (32%). Response rate was 10%; a further 40% of patients achieved stable disease. All responses were observed in patients with ECOG PS < or = 1, age <70 years, and who had received only one prior chemotherapy regimen. Median time to progression was 2.8 months and median survival was 7.4 months. Because of significant toxicity and limited activity, further investigation of irinotecan plus docetaxel in second line NSCLC is not recommended.