Practice Patterns and Outcomes for Pemetrexed Plus Platinum Doublet as Neoadjuvant Chemotherapy in Adenocarcinomas of Lung: Looking Beyond the Usual Paradigm.

AIMS: Neoadjuvant chemotherapy (NACT) is the standard of care in non-small cell lung cancers (NSCLC) with locally advanced N2 disease. There is a scarcity of data for the pemetrexed-platinum regimen as NACT. Also, apart from N2 disease, the role of NACT in locally advanced NSCLCs for tumour downstaging is unclear. MATERIALS AND METHODS: Non-metastatic adenocarcinomas of lung treated with pemetrexed-platinum-based NACT were analysed. The patients with locoregionally advanced N2 disease and those who were borderline candidates for upfront definitive treatment were planned for NACT after discussion in a multidisciplinary clinic. In total, four cycles of 3-weekly pemetrexed and platinum were delivered in the combined neoadjuvant and adjuvant setting. A response assessment was carried out using RECIST criteria. Progression-free (PFS) and overall survival were calculated using the Kaplan-Meier method. RESULTS: Of 114 patients, 96 evaluable patients received NACT with pemetrexed-platinum. The most common indication for NACT was N2 disease at baseline (46.8%). The objective response rate was 36.4% (95% confidence interval 22-52%), including two complete and 32 partial responses, whereas 12.5% of patients had progressive disease on NACT. The median PFS was 14 months (95% confidence interval 10.7-17.3) and the median overall survival was 22 months (95% confidence interval 15.6-28.4) at a median follow-up of 16 months. There was a significant improvement in the overall survival of patients undergoing definitive therapy versus no definitive therapy (median overall survival 25 months [95% confidence interval 19.6-30.4] versus 12 months [95% confidence interval 3.2-20.7], respectively; P = 0.015, hazard ratio 0.56 [95% confidence interval 0.3-0.9]). Among patients who could not undergo definitive chemoradiation upfront due to dosimetric constraints (n = 34), 24 (70.6%) patients finally underwent definitive therapy after NACT. CONCLUSIONS: Pemetrexed-platinum-based NACT seems to be an effective option and many borderline cases, where upfront definitive therapy is not feasible, may become amenable to the same after incorporation of NACT.

Repeat biopsy in epidermal growth factor receptor mutation-positive nonsmall cell lung cancer: Feasibility, limitations, and clinical utility in Indian patients.

INTRODUCTION: The feasibility and success rate of repeat biopsy for epidermal growth factor receptor (EGFR) mutation-positive lung cancers that have progressed on tyrosine kinase inhibitors (TKIs) are varied and merits further assessment. MATERIALS AND METHODS: EGFR mutation-positive lung cancers were offered repeat biopsy upon progression on TKIs. Two groups of patients, first one on a clinical trial and second one from a database, were included for analysis. The feasibility to perform a repeat biopsy was analyzed in the first group. Success rate of biopsy and tissue adequacy for molecular testing was analyzed in both groups. Descriptive statistics were used for analyzing the demography, EGFR mutation type, tissue adequacy, and molecular profile at repeat biopsy. Kolmogorov-Smirnov test was used to assess normality of data. Two sample t-tests were used for comparison of proportions. RESULTS: The feasibility of undergoing repeat biopsy was 77% (95% confidence interval [CI] of 69.4%-83.5%) in the first group (114/148 patients). Feasibility was not analyzed in the second group of patients. Out of 196 patients who underwent a repeat biopsy, 154 patients (78.6%; 95% CI: 72.2%-84.1%) had tumor tissue adequate for performing molecular testing. 27/196 (13.8%) patients did not have any evidence of malignancy on repeat biopsy whereas 15/196 (7.6%) patients had scanty tissue on repeat biopsy prohibiting molecular testing. Six patients (3.06%; 95% CI: 1.1%-6.5%) had small cell transformation. T790M mutation was detected in 12 out of the 42 patients (28.6%; 95% CI: 15.7-44.6) in whom EGFR testing was performed on repeat biopsy specimen. CONCLUSION: Repeat biopsy was able to provide adequate tissue acquisition in only two-thirds of the patients. Liquid biopsy represents an important tool to bridge this gap.

Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first-line chemotherapy from a tertiary cancer center in India.

INTRODUCTION: Unlike the developed countries, there is a lack of good epidemiologic data for testicular germ cell tumors (GCTs) in India with majority presenting in advanced stage. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard first-line chemotherapy (CT). METHODS: GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (bleomycin, etoposide, and cisplatin/etoposide and cisplatin/carboplatin AUC7) and radiotherapy were given as appropriate. Response was calculated based on the Response Evaluation Criteria in Solid Tumors. Statistical analysis was performed using SPSS 18 software. RESULTS: Fifty nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5-19) in NSGCT and 5.5 cm (1.3-11) in SGCT. As per the International Germ Cell Cancer Collaborative Group classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia, Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. CONCLUSIONS: GCTs in India present with high nodal and high-risk diseases wherein the standard first-line CT may not be adequate as curative therapy; however, significant chemotoxicity is also a hindrance.

Patterns of care and outcomes for second-line targeted therapy in metastatic renal cell carcinomas: A registry based analysis.

AIM: Patterns of care for metastatic renal cell carcinomas (mRCC) have seen tremendous reform in the last decade. Here, we present our pattern of care in second-line targeted therapy for mRCC. METHODS: Patients with mRCC treated with second-line therapy were included from a prospective database. Demographics, risk stratification, and treatment details were noted. Event-free survival (EFS) and overall survival (OS) was calculated using Kaplan-Meier method. Log-rank test was used to identify factors affecting EFS and OS. Multivariate analysis was performed using cox regression. RESULTS: Nearly 21.7% (46/212) of patients received second-line targeted treatment. Heng score for risk stratification showed 21.7% of patients in low risk, 36.9% in intermediate, and 34.8% in high risk group. Everolimus followed by pazopanib were the most common second-line therapies used in 65.2% and 13% of patients, respectively. The estimated median EFS was 3.5 months (95% confidence interval [CI] 2.7-4.26 months) and estimated median OS from the start of second-line therapy was 6.2 months (95% CI 3.4-9.0 months) with a median follow-up of 4.3 months. On univariate log-rank analysis, EFS of more than 6 months with first-line therapy was associated with improvement in EFS with second-line therapy (9.5 vs. 2.0 months; hazard ratio (HR) 0.364; P = 0.002). There was no factor independently associated with EFS or OS on multivariate analysis. CONCLUSION: Patterns of care for second line targeted therapy tend to vary with setting. A longer EFS with first-line therapy predicts improved outcomes with second-line treatment.