Metastatic Bladder Cancer: Second-Line Treatment and Recommendations of the Genitourinary Tumor Division of the Galician Oncologic Society (SOG-GU).

Once metastatic bladder cancer has progressed to first-line treatment, the number of therapeutic options is scarce. Among chemotherapeutic agents showing activity in phase II trials, including taxanes, vinflunine (VFL) is the only one shown to increase overall survival in a phase III trial. In addition to its efficacy, VFL is safe in special population groups. Despite this, the prognosis for these patients remains poor, and more effective therapies need to be developed. Agents acting on new therapeutic targets as well as biomarkers to aid matching patients to specific treatments are currently under evaluation. In this regard, immunotherapy is showing promising results. In this article, a critical review of current treatments and future prospects is made, and therapy recommendations are made based on existing scientific evidence.

Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking.

Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician Lung Cancer Group.

BACKGROUND: In clinical studies, first-line afatinib demonstrated efficacy in Del19-EGFR NSCLC. MATERIALS AND METHODS: This prospective, non-interventional study assessed efficacy and safety of first-line afatinib in patients with advanced/metastatic NSCLC with Del19-EGFR from Galicia (Spain), with a preplanned analysis by age (<70 vs ≥70 years). RESULTS: Median age of 46 patients enrolled was 69.5 years (range 37-87). The objective response rate (ORR) was 78.2%, with median progression-free survival (PFS) of 20.5 months (95% CI 12.7, 28.3) and median overall survival (OS) of 37.5 months (95% CI 19.2-55.8). Outcomes by age (<70 vs ≥70 years) were ORR of 82.6% vs 73.9%, median PFS of 20.2 months (95% CI 14.8-25.6) vs 24.1 (9.8-38.3), and median OS of 45.1 months (95% CI, 17.0-73.1) vs 33.9 (28.7-39.1), respectively. Median treatment duration was 17.2 months (range 0.4-64.1) with 11 patients still on treatment; 14 patients received osimertinib at discontinuation due to T790M. Grade 3 adverse events included mucositis (n = 7, 15.2%), skin toxicity (n = 9, 19.6%), and diarrhea (n = 6, 13.0%) that were manageable with dose reductions. The afatinib dose was reduced in 31 patients (67.4%) and treatment was discontinued in 8 patients (17.4%) due to adverse events. By age (<70 vs ≥70 years), afatinib was dose-reduced in 13 (56.5%) vs 18 patients (78.3%) and discontinued in 3 (13.0%) vs 5 patients (21.7%), respectively. CONCLUSIONS: PFS in our patients was longer than reported in clinical studies with similar response rates and toxicity, even in older patients, reflecting a good risk-benefit from afatinib in patients with Del19-EGFR NSCLC. MICROABSTRACT: This real-world study of first-line afatinib in Caucasian patients with Del19 EGFR NSCLC reported durable efficacy and showed that older patients (> 70 years) benefitted from afatinib as much as younger patients. The safety profile of afatinib was as expected, albeit more dose reductions in older patients. Afatinib may be an option for patients with Del19 EGFR NSCLC, even in those who are older.

Evaluation of the lung immune prognostic index in advanced non-small cell lung cancer patients under nivolumab monotherapy.

The lung immune prognostic index (LIPI) has been proposed as a new categorical blood-based biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) therapy. In this study, we investigate for the first time to the best of our knowledge the prognostic and predictive utility of the LIPI in a multicenter nivolumab monotherapy-based cohort. We retrospectively analyzed the influence of the baseline LIPI on overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and overall response rate (ORR) among 153 patients of a cohort of 188 advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond. Worse LIPI was significantly associated with shorter OS in univariate [hazard ratio (HR) =3.12, 95% confidence interval (CI), 2.12-4.60; P<0.0001] and multivariate (HR =3.67, 95% CI, 1.96-6.86; P<0.0001) analyses. Worse LIPI was associated with shorter PFS (HR =1.45, 95% CI, 1.05-2.03; P=0.03), but this correlation did not reach statistical significance in multivariate analysis (HR =1.49, 95% CI, 0.94-2.38; P=0.09). Worse LIPI was associated with lower DCR in univariate [odds ratio (OR) =0.41, 95% CI, 0.24-0.70; P=0.001] and multivariate (OR =0.44, 95% CI, 0.25-0.78; P=0.005) analyses. This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

Fluorescence in situ hybridization analysis of the ALK gene in 2,045 non-small cell lung cancer patients from North-Western Spain (Galicia).

Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.

Enzalutamide: a new prostate cancer targeted therapy against the androgen receptor.

Enzalutamide (MDV3100), an androgen receptor-signalling inhibitor, represents the most recent compound added to the therapeutic armamentarium for the treatment of metastatic castration-resistant prostate cancer (mCRPC) who progressed to docetaxel. The anti-tumour activity and safety of enzalutamide has been demonstrated in a phase III clinical trial, showing a benefit in overall survival, which was the primary endpoint. There are no head-to-head studies comparing the different treatment options in this subset of patients. In this article, most relevant data published in the literature have been reviewed, with special attention to the therapeutic alternatives currently available for postdocexatel mCRPC patients, emphasising the mechanisms of action of the different drugs, efficacy and quality of life-related aspects.

First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients.

OBJECTIVE: The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC). RESEARCH DESIGN AND METHODS: Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method. RESULTS: Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5) and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%) experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia nor toxic death was observed. CONCLUSIONS: The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.