Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(?) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(?) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

     

Usefulness of the Spanish version of the mood disorder questionnaire for screening bipolar disorder in routine clinical practice in outpatients with major depression

Background

According to some studies, almost 40% of depressive patients – half of them previously undetected – are diagnosed of bipolar II disorder when systematically assessed for hypomania. Thus, instruments for bipolar disorder screening are needed. The Mood Disorder Questionnaire (MDQ) is a self-reported questionnaire validated in Spanish in stable patients with a previously known diagnosis. The purpose of this study is to evaluate in the daily clinical practice the usefulness of the Spanish version of the MDQ in depressive patients.

Methods

Patients (n = 87) meeting DSM-IV-TR criteria for a major depressive episode, not previously known as bipolar were included. The affective module of the Structured Clinical Interview (SCID) was used as gold standard.

Results

MDQ screened 24.1% of depressive patients as bipolar, vs. 12.6% according to SCID. For a cut-off point score of 7 positive answers, sensitivity was 72.7% (95% CI = 63.3 – 82.1) and specificity 82.9% (95% CI = 74.9–90.9). Likelihood ratio of positive and negative tests were 4,252 y 0,329 respectively.

Limitations

The small sample size reduced the power of the study to 62%.

Conclusion

Sensitivity and specificity of the MDQ were high for screening bipolar disorder in patients with major depression, and similar to the figures obtained in stable patients. This study confirms that MDQ is a useful instrument in the daily clinical assessment of depressive patients.

     

Once-Daily Triple Therapy in Patients with Advanced COPD: Healthcare Resource Utilization Data and Associated Costs from the FULFIL Trial

Introduction

Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.

Methods

FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study. Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.

Results

Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%). Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs. 32.7%). Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs. £763.32 and £749.22 vs. £988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs. £1,267.45).

Conclusions

This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.

Trial Registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK

     

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study)

Introduction

Heart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.

Methods

This multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.

Results

At the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).

Conclusion

In patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.

Trial Registration

ISRCTN30654443.

Funding

Servier.

     

Automatic classification of lung nodules on MDCT images with the temporal subtraction technique

Purpose

A temporal subtraction (TS) image is obtained by subtracting a previous image, which is warped to match the structures of the previous image and the related current image. The TS technique removes normal structures and enhances interval changes such as new lesions and substitutes in existing abnormalities from a medical image. However, many artifacts remaining on the TS image can be detected as false positives.

Method

This paper presents a novel automatic segmentation of lung nodules using the Watershed method, multiscale gradient vector flow snakes and a detection method using the extracted features and classifiers for small lung nodules (20 mm or less).

Result

Using the proposed method, we conduct an experiment on 30 thoracic multiple-detector computed tomography cases including 31 small lung nodules.

Conclusion

The experimental results indicate the efficiency of our segmentation method.

     

Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis

Objective

To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis.

Design

Prospective study.

Setting

The paediatric intensive care unit of a university hospital.

Patients

Twelve infants less than 3 months of age, with severe respiratory distress.

Interventions

Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients.

Measurements and results

The respiratory distress score decreased after nCPAP, particularly accessory muscles’ use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes_insp, two indices of inspiratory effort, were reduced by 54 (±4)% and 59 (±5)%. PTPgas_exp, an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP.

Conclusions

In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms.

     

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Purpose

During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures

Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.

Results

The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30 % of mice with positive margins. Molecular imaging identified an additional 50 % of residual tumor deposits (p?<?0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.

Conclusions

Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

     

Concurrent Improvement in Both Binge Eating and Depressive Symptoms with Naltrexone/Bupropion Therapy in Overweight or Obese Subjects with Major Depressive Disorder in an Open-Label,Uncontrolled Study

Introduction

Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms.

Methods

This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms.

Results

At baseline, 91% of subjects had moderate or severe BES scores, suggesting BED. BES scores were significantly improved from week 4, and by week 24, 83% reported “little or no problem.” Improvement in BES scores correlated with improvement in depressive symptoms and control of eating.

Conclusion

NB may be effective in reducing binge eating symptoms associated with MDD and overweight/obesity. Evaluation of NB in BED appears warranted.

Funding

Orexigen Therapeutics, Inc.

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

Création d’un programme d’éducation thérapeutique en douleur chronique (PETDC) — Expérience Canadienne

Aims

Create an educational program in chronic pain (EPCP).

Material and methods

We used a four-step process to create the EPCP tailored to patient’s needs.

Results

Five groups of patients can benefit from the program annually. Based on their own assessment, patients stated that their knowledge of chronic pain improved between 2.8 to 24%. The satisfaction with the EPCP was 8.67/10.

Conclusion

Our EPCP helps patients gain and maintain the skills they need to best manage their lives with a chronic pain.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up

Introduction

The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.

Methods

Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.

Results

At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.

Conclusion

In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.

Trial Registration

ClinicalTrials.gov identifier, NCT02868190.

Funding

Glaukos Corporation, San Clemente, CA.

     

Impact of Region-of-Interest Delineation Methods,Reconstruction Algorithms,and Intra- and Inter-Operator Variability on Internal Dosimetry Estimates Using PET

Purpose

Human dosimetry studies play a central role in radioligand development for positron emission tomography (PET). Drawing regions of interest (ROIs) on the PET images is used to measure the dose in each organ. In the study aspects related to ROI delineation methods were evaluated for two radioligands of different biodistribution (intestinal vs urinary).

Procedures

PET images were simulated from a human voxel-based phantom. Several ROI delineation methods were tested: antero-posterior projections (AP), 3D sub-samples of the organs (S), and a 3D volume covering the whole-organ (W). Inter- and intra-operator variability ROI drawing was evaluated by using human data.

Results

The effective dose estimates using S and W methods were comparable to the true values. AP methods overestimated (49 %) the dose for the radioligand with intestinal biodistribution. Moreover, the AP method showed the highest inter-operator variability: 11 ± 1 %.

Conclusions

The sub-sampled organ method showed the best balance between quantitative accuracy and inter- and intra-operator variability.

     

Can strain elastography combined with ultrasound breast imaging reporting and data system be a more effective method in the differentiation of benign and malignant breast lesions?

Purpose

To investigate whether a novel method that combines breast imaging reporting and data system (BI-RADS) with strain elastography contributes to diagnostic performance in differentiation of malignant and benign breast lesions.

Methods

In 81 patients, 81 breast lesions were prospectively investigated. Breast lesions were separately evaluated with ultrasonography and strain elastography. While evaluations with ultrasonography were based on 2003 BI-RADS-US, strain elastography evaluations were based on a 5-point scale and strain ratio. Diagnostic performances of ultrasonography, strain elastography, and the combined method were compared.

Results

Among 81 lesions, 43 (53.1%) were benign and 38 (46.9%) were malignant. When a cutoff point of category 3 was used, sensitivity, specificity, positive and negative predictive values, and accuracy for BI-RADS were 100, 11.6, 50, 100, and 53%, respectively. When BI-RADS and strain ratio were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 89.5, 93, 91.9, 90.9, and 91.3%, respectively. When BI-RADS and elastography scores were combined, sensitivity, specificity, positive and negative predictive values, and accuracy were 86.8, 97.7, 97.1, 89.4, and 92.5%, respectively.

Conclusions

The combination of strain elastography and BI-RADS was found to have better diagnostic performances to diagnose breast lesions than BI-RADS alone.

     

Sekundäre Steife der Schulter

Background

In addition to idiopathic shoulder stiffness, secondary shoulder stiffness in particular is often associated with extra-articular subacromial adhesions between the rotator cuff and the surrounding anatomical structures.

Objective

The aim of this article is to present clinical results and complications as well as the surgical technique of extra-articular release in the context of secondary shoulder stiffness.

Material and Methods

Selective review of the literature and presentation of own clinical experience.

Results

Intra-articular and extra-articular release are related to a high patient satisfaction and an improved range of motion. Exact knowledge of the extra-articular anatomy is necessary to prevent iatrogenic lesions of vessels, nerves and the rotator cuff. Compared to patients with a primary stiff shoulder, patients suffering from posttraumatic stiff shoulder benefit more from arthroscopic interventions with intracapsular and extracapsular release.

Conclusion

Restrictions in range of motion of the shoulder can be related to extra-articular adhesions. These adhesions need to be specifically addressed during arthroscopic treatment of stiff shoulders.

     

Focal hepatic solid lesions incidentally detected on initial ultrasonography in 542 asymptomatic patients

Purpose

The purpose of this study is to evaluate the clinical significance of focal hepatic solid lesions incidentally detected on initial ultrasonography in asymptomatic patients.

Methods

From January 2009 to December 2009, 2670 initial ultrasonographies were performed in asymptomatic population. Of these 2670 initial examinations, 681 focal hepatic solid lesions in 542 patients (mean 39.4 years, range 23–73 years) were detected. Clinical information, ultrasonography features, and the outcome of these lesions were analyzed.

Results

Six hundred and seventy four lesions (99.0%) in 539 patients (99.4%) were benign, while seven lesions (1.0%) in three patients (0.6%) proved to be malignant. Risk factors significantly associated with malignant focal hepatic solid lesions were known history of malignancy, history of hepatitis, a positive result for the hepatitis B surface antigen, and abnormally elevated tumor markers. No malignancy was identified in patients without any one of these four risk factors. Ultrasonographic features of internal heterogeneous echotexture with peripheral hypoechoic rim showed significant associations with malignancy.

Conclusions

Focal hepatic solid lesions incidentally detected on initial ultrasonography were rarely malignant, especially in patients without these risk factors. Therefore, the knowledge of these risk factors and US features is important in order to make a differential diagnosis between benign and malignant focal hepatic lesions.

     

Comprehensive preclinical evaluation of a multi-physics model of liver tumor radiofrequency ablation

Purpose

We aim at developing a framework for the validation of a subject-specific multi-physics model of liver tumor radiofrequency ablation (RFA).

Methods

The RFA computation becomes subject specific after several levels of personalization: geometrical and biophysical (hemodynamics, heat transfer and an extended cellular necrosis model). We present a comprehensive experimental setup combining multimodal, pre- and postoperative anatomical and functional images, as well as the interventional monitoring of intra-operative signals: the temperature and delivered power.

Results

To exploit this dataset, an efficient processing pipeline is introduced, which copes with image noise, variable resolution and anisotropy. The validation study includes twelve ablations from five healthy pig livers: a mean point-to-mesh error between predicted and actual ablation extent of 5.3 ± 3.6 mm is achieved.

Conclusion

This enables an end-to-end preclinical validation framework that considers the available dataset.

     

Contrast-enhanced ultrasound for needle biopsy of central lung cancer with atelectasis

Purpose

Contrast-enhanced ultrasound (CEUS) can distinguish between central lung cancer and atelectatic lung tissue. The aim of this study was to explore the clinical value of CEUS for biopsy in patients with central lung cancer with obstructive atelectasis.

Methods

One hundred and twelve patients were selected and CEUS was performed to display central lung cancer and atelectatic lung tissue. The front edge of central lung cancer was punctured with a needle, avoiding the necrotic area, under the guidance of CEUS.

Results

All of the 112 lesions were diagnosed with a clear central lung cancer mass and atelectatic lung tissue. In 104 cases, the central lung cancer mass presented with a “slow-in and fast-out” pattern compared to atelectatic lung tissue. In eight cases, the central lung cancer mass presented with a “fast-in and fast-out” pattern compared to atelectatic lung tissue. The mean number of punctures was 2.6, and the success rate of puncture biopsy was 98%. Of the 112 patients, six cases had hemoptysis during the procedure and 10 patients had bloody sputum in the postoperative period. No complications were found in the other cases.

Conclusion

CEUS has important clinical value for needle biopsy of central lung cancer with atelectasis.

     

Monitoring for and Characterizing Crizotinib Progression: A Chart Review of <Emphasis Type="Italic">ALK</Emphasis>-Positive Non-Small Cell Lung Cancer Patients

Introduction

Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib.

Methods

A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March–June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib.

Results

A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3–4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy.

Conclusion

The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib.

Funding

Novartis Pharmaceuticals Corporation.