In this prospective phase III trial, afatinib combined with paclitaxel improved progression-free survival and objective response, compared with single-agent chemotherapy, in patients with NSCLC who were clinically enriched for ErbB dependency having failed platinum-based chemotherapy, gefitinib/erlotinib and afatinib monotherapy after initial benefit on each tyrosine kinase inhibitor.

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ABSTRACT. Different forms of p210 are produced by alternative splicing, namely b2a2 and b3a2. There have been many contrasting data establishing a relationship between the two Bcr/Abl transcripts and platelet counts and also response to treatment. However, the data published to date have been on a small group of patients. The aim of the present study was to determine whether there was any difference between clinical and hematological parameters at diagnosis between the two Bcr/Abl fusion transcripts in our population, and whether the two transcripts responded differently or similarly to imatinib treatment. RT-PCR was performed in 202 cases for detection of Bcr/Abl transcripts in newly diagnosed chronic myelogenous leukemia cases in one year. The two transcripts were compared and correlated with clinical, hematological and FISH data and with response to treatment. A total of 138 cases were of b3a2 and 64 were of b2a2 transcript. There was no correlation between the hemato- logical parameters and the type of transcript. There was a significant association of blast crisis with b2a2, especially with myeloid blast crisis. When compared to FISH results, 10% of b3a2 were found to have a significant association with 5'Abl deletion as compared to 3% of b2a2. On analyzing the therapeutic response, we did not find any difference between the two transcripts. In conclusion, our findings confirm that the b3a2 type transcript is not significantly associated with thrombocytosis, that the short transcript, b2a2, occurs with acute phase, i.e., blast crisis, and that there is no difference in treatment response between the two transcripts. However, further studies are required to understand the molecular pathways involved in the Bcr/Abl mechanism.

The repeatability and reproducibility of radiomic features extracted from CT scans need to be investigated to evaluate the temporal stability of imaging features with respect to a controlled scenario (test–retest), as well as their dependence on acquisition parameters such as slice thickness, or tube current. Only robust and stable features should be used in prognostication/prediction models to improve generalizability across multiple institutions. In this study, we investigated the repeatability and reproducibility of radiomic features with respect to three different scanners, variable slice thickness, tube current, and use of intravenous (IV) contrast medium, combining phantom studies and human subjects with non-small cell lung cancer. In all, half of the radiomic features showed good repeatability (ICC > 0.9) independent of scanner model. Within acquisition protocols, changes in slice thickness was associated with poorer reproducibility compared to the use of IV contrast. Broad feature classes exhibit different behaviors, with only few features appearing to be the most stable. 108 features presented both good repeatability and reproducibility in all the experiments, most of them being wavelet and Laplacian of Gaussian features.

Background There are limited data available on the treatment and outcome of epidermal growth factor receptor (EGFR) exon 20-mutated lung cancer patients. Hence, we planned an analysis of the demographic details, clinical profile and survival of lung cancer patients with exon 20 mutations. We compared our results to patients with EGFR tyrosine kinase inhibitor (TKI)-sensitizing activating and EGFR/anaplastic lymphoma kinase (ALK)-negative mutations. Methods This was a retrospective analysis of lung cancer patients who were treated at our center between January 2010 and August 2014. We reviewed the results of EGFR mutation testing by real-time polymerase chain reaction and Sanger sequencing. We also reviewed the data relating to baseline demographics, clinical profile, patient treatment and outcome measures in terms of response and overall survival (OS). Results A total of 580 patients fulfilled the selection criteria. In all, 227 (39.1%) patients had EGFR TKI-sensitizing activating mutations, 20 (3.4%) patients had exon 20 insertion mutations and 333 patients were EGFR/ALK mutation negative (57.5%). The median OS was 5 months (95% confidence interval [CI] 0.17–9.8 months) in exon 20 insertion mutations, 16.1 months (95% CI 12.8–19.5 months) in EGFR TKI-sensitizing activating mutations and 10 months (95% CI 7.9–12.1 months) in EGFR/ALK mutation-negative patients. The median OS was significantly better for the EGFR TKI-sensitizing activating mutation group ( P =0.000, log-rank test) and for the EGFR/ALK-negative group ( P =0.037, log-rank test) compared to the exon 20-mutated group. Conclusion Exon 20 mutation results in a poorer OS prognosis compared to EGFR- and ALK-negative patients and patients harboring EGFR TKI-sensitizing activating mutations. The incidence of de novo exon 20 insertions was 3.4%. Different types of exon mutations seem to have different outcomes.

Introduction ROS1 oncogenic fusion, which was first identified by Rikova et al, is reported to be present in 1%–2% of non-small cell lung cancers (NSCLCs) and is defined as a distinct molecular sub-group. Crizotinib is very effective in ROS1-positive patients and is now Food and Drug Administration (FDA) approved for the treatment of patients with advanced ROS1-positive NSCLC. We report our experience in a tertiary cancer care hospital in India in ROS-1 positive patients. Materials and method The present series is a retrospective analysis of 22 patients from the prospectively maintained lung cancer audit. Demographic data were collected which included age, performance status, gender, stage, co-morbidities, sites of metastasis and smoking history. Data were also collected regarding the source of financing for crizotinib whether self-financed, through insurance or Non-Governmental Organisation (NGO) sponsored. Patients who had tested negative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and were subsequently found to be ROS1-mutation negative by fluorescence in situ hybridization (FISH) were evaluated on similar lines. All the data were entered and statistical analyses were performed using the SPSS software version 22.0. Response evaluation was done by RECIST 1.1 criteria. Results Between January 2015 and December 2017, there were 22 patients who were ROS1 positive from a total of 535 patients in whom ROS1 testing was performed. A total of 16 patients could receive crizotinib and 6 patients were never exposed to crizotinib. Among the 16 patients who received crizotinib, 2 (12.5%) achieved complete response (CR) as their best response and continue to remain in CR at follow-up. 13 (81%) had a partial response as best response and of which on follow-up 5 (38%) have progressed, while 8 (62%) continue to maintain response. The patients who were on crizotinib had good tolerance with none experiencing any grade 3/4 toxicity. The median follow-up of the entire cohort was 15.2 months in ROS1-positive cohort and 11.4 months in ROS1-negative cohort. In ROS1-positive cohort median, progression-free survival (PFS) was not reached and the estimated 2-year PFS was 54% and in ROS1-negative cohort, it was 5.1 months. The median overall survival of the entire ROS1-positive cohort was not reached and the estimated 1- and 2-year overall survival (OS) was 72% and 54%, respectively, and was 8.8 months in ROS1-negative cohort. Conclusion ROS1 rearrangement with an incidence of 4% of lung adenocarcinoma which is EGFR and ALK negative represents an important targetable driver mutation in the Indian population. Crizotinib also represents an effective treatment option with outcomes similar to those reported. Access to treatment remains an important roadblock to improve outcomes but innovative methods may improve access to these drugs.

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BackgroundThe purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.MethodsThis multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min) every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response). Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.ResultsThe objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04). A complete response and partial response were achieved in 3.6% and 50% of patients, respectively, in the nimotuzumab group, and in 4% and 30.9% of patients, respectively, in the control group. No significant differences in median progression-free survival and overall survival were observed. Safety profiles were comparable between the two groups.ConclusionNimotuzumab plus chemotherapy significantly improved the objective response rate as compared with chemotherapy alone. The combination was safe and well tolerated in patients with stage IIIB/IV non-small-cell lung cancer.