Quality of life with second or third line nab-paclitaxel-based regimens in advanced non-small-cell lung cancer.

Aim: Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods: Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results: QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19-56% and 9-51% of patients, respectively. Conclusion: While QoL trends were promising, additional data are required to support these regimens in this setting.

Analysis of Patients Unable to Undergo Adjuvant Chemotherapy after Surgery in Stage IIIA/B Non-Small Cell Lung Cancer: Will They Benefit from Mediastinal Radiotherapy?

Objectives The role of postoperative mediastinal radiotherapy in completely resected non-small cell lung cancer (NSCLC) and pathological N2 disease is controversial. In clinical practice, not all lung cancer patients with histologically confirmed N2 disease and a high risk for local recurrence are able to undergo postoperative concurrent radio/chemotherapy due to their physical condition or postoperative morbidities. Mediastinal radiotherapy is less compromising than a combination of radio/chemotherapy and seems likely to be tolerable for limited patients to achieve better local tumor control. Materials and Methods All patients included in this retrospective analysis were excluded from postoperative adjuvant combination chemo/radiotherapy due to their comorbidity, advanced age, or a complicated postoperative course. Three-dimensional conformal radiotherapy of the mediastinal lymph node stations (mean dose: 50 Gy; range: 50-54 Gy) in patients with R0 resection, additional boost of 10 Gy in patients with R1 or R2 resection, was performed postoperatively. Results A total of 110 patients were included in this analysis. Mean survival was 25.5 ± 19.2 months. The 1-, 3-, and 5-year survival was 75.4, 38.7, and 26.2%, respectively. Postoperative complications and the development of distant metastases did not correlate (p = 0.7). Distant metastases proved to be a significant prognostic factor of survival (p < 0.0001). Local recurrence was seen in a total of three patients (2.7%). Five-year survival of patients developing major postoperative complications was significantly inferior (p = 0.04) to those without postoperative complications. The extent of surgery had a significant impact on survival-5-year survival after lobectomy was significantly longer than after pneumonectomy (p = 0.029). R1 resection had no significant impact on the survival rates (p = 0.67). Discussion Stage III-N2 NSCLC patients with multiple comorbidities or a complicated postoperative course after surgery may benefit from modern mediastinal radiotherapy. Surgery and postoperative mediastinal radiotherapy can achieve local tumor control. Distant metastases have the highest impact on the prognosis. Pneumonectomy, however, should be avoided in stage III NSCLC, when possible.

Cabazitaxel Versus Topotecan in Patients with Small-Cell Lung Cancer with Progressive Disease During or After First-Line Platinum-Based Chemotherapy.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) typically respond well to initial chemotherapy. However, relapse invariably occurs, and topotecan, the only approved second-line treatment option, has limited efficacy. Taxanes have activity in SCLC, and cabazitaxel is a second-generation taxane with potential for enhanced activity in chemorefractory malignancies. METHODS: Patients with SCLC who relapsed after initial platinum-based chemotherapy were randomly assigned to receive cabazitaxel 25 mg/m every 21 days or topotecan 1.5 mg/m on days 1-5 every 21 days. Two patient subgroups, defined by chemosensitive and chemo-resistant/refractory disease, were assessed in combination and separately. RESULTS: The safety profile of cabazitaxel and topotecan was consistent with previous studies, and despite considerable toxicity in both arms, no new safety concerns were identified. Patients receiving cabazitaxel had inferior progression-free survival compared with topotecan (1.4 versus 3.0 months, respectively; two-sided p < 0.0001; hazard ratio = 2.17, 95% confidence interval = 1.563-3.010), and results were similar in both the chemosensitive and chemorefractory subgroups. No complete responses were observed in either arm, and no partial responses were observed in the cabazitaxel group. The partial response rate in the topotecan arm was 10%. Median overall survival was 5.2 months in the cabazitaxel arm and 6.8 months in the topotecan arm (two-sided p = 0.0125; hazard ratio = 1.57, 95% confidence interval = 1.10-2.25). CONCLUSION: Cabazitaxel, a next-generation taxane, had inferior efficacy when compared with standard-dose topotecan in the treatment of relapsed SCLC. Topotecan remains a suboptimal therapy, and continued efforts to develop improved second-line treatments are warranted.

EGFR mutation status and first-line treatment in patients with stage III/IV non-small cell lung cancer in Germany: an observational study.

INTRODUCTION: EGFR mutations confer sensitivity to EGFR tyrosine kinase inhibitors (TKI) in advanced non-small cell lung cancer (NSCLC). We investigated the clinicopathologic characteristics associated with EGFR mutations and their impact on real-world treatment decisions and outcomes in Caucasian patients with advanced NSCLC. METHODS: REASON (NCT00997230) was a noninterventional multicenter study in patients (≥18 years) with stage IIIb/IV NSCLC, who were candidates for EGFR mutation testing and first-line systemic treatment, but not eligible for surgery or radiotherapy. Patients were followed up according to normal clinical practice and assessed for primary (correlation of mutation status with baseline characteristics) and secondary endpoints (first-line treatment decision). RESULTS: Baseline data were obtained for 4,200 patients; 4,196 fulfilled the inclusion criteria; EGFR mutations were detected in 431 patients; no EGFR mutations were detected in 3,590 patients; mutation status was not evaluable in 175 patients. In multivariate analysis, the odds of EGFR mutations were significantly higher (P < 0.0001) in females versus males (odds ratio: 1.85; 95% confidence interval, 1.48-2.32), never-smokers versus smokers (3.64; 2.91-4.56), and patients with adenocarcinoma versus other histologic subtypes (2.94; 2.17-4.08). The most commonly prescribed first-line systemic treatments were: EGFR-TKIs in EGFR mutation-positive NSCLC (56.6%) and combination chemotherapy in EGFR mutation-negative NSCLC (78.5%). CONCLUSIONS: This represents the largest dataset for EGFR mutations in Caucasian patients and shows EGFR mutations to be most prevalent in females with adenocarcinoma who had never smoked. IMPACT: These findings add to our understanding of the prognostic and predictive factors of NSCLC, supporting future improved treatment selection.

Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer.

PURPOSE: We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). RESULTS: Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). CONCLUSION: This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients.

Tasisulam sodium (LY573636 sodium) as third-line treatment in patients with unresectable, metastatic non-small-cell lung cancer: a phase-II study.

INTRODUCTION: Tasisulam sodium (hereafter referred to as tasisulam) is a novel anticancer compound that induces apoptosis and exhibits antiangiogenesis activity in a broad range of cancer models, including non-small-cell lung cancer (NSCLC). METHODS: Tasisulam was administered as a 2-hour infusion every 21 days as third-line treatment in patients with advanced (stage IIIB/IV) NSCLC. RESULTS: Thirty-two patients received a Cmax target dose of 420 µg/ml. Median time to progression was 3.12 months, median progression-free survival was 2.69 months, and median overall survival was 8.48 months. There were no objective responses; 43.8% of patients achieved stable disease. A high rate of grade-4 hematologic toxicity in the first 30 patients led to exploration of a lower Cmax target dose of 380 µg/ml. The rate of grade-4 hematologic toxicity (thrombocytopenia and/or neutropenia) at the 380-µg/ml dose (n = 20) was 20% versus 34% at the 420-µg/ml dose. CONCLUSIONS: Tasisulam has only modest activity as a third-line treatment of patients with unresectable/metastatic NSCLC. The high rate of grade-4 hematologic toxicity observed with this highly albumin- bound compound in this patient population provided challenges for fixed Cmax-based dosing. Alternative dosing methods, including varying the Cmax target dose by predose albumin, are under investigation in other studies.