Background Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. MethodsWe did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m² methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. Findings Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-totreat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15•73 months, median overall survival in the intention-to-treat analysis population was 7•5 months (IQR 4•6-12•6) in the oral metronomic chemotherapy group compared with 6•1 months (3•2-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•773 [95% CI 0•615-0•97, p=0•026]). In the per-protocol analysis population, median overall survival was 7•5 months (4•7-12•8) in the oral metronomic chemotherapy group and 6•1 months (3•4-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•775 [95% CI 0•616-0•974, p=0•029]). Grade 3 or highe...
Background: Management of brain metastasis is a complex multidisciplinary venture. Hence, we started a multidisciplinary brain metastasis clinic for the opinion on difficult brain metastasis cases. This is the review of the impact of this clinic on the treatment decisions. Methods: The brain metastasis clinic (BMC) was started in April 2018 and meets once a week. Data of patients discussed between 27th April 2018 and 28th June 2019 were included for this analysis. Treatment decision made by clinicians (before sending the patient to the BMC) was compared with the decisions made in BMC. The decisions were broken on a predefined proforma as the intent of treatment (curative or palliative), modalities planned (surgery, radiation, chemotherapy) and type of therapy planned (details of each therapy) in each modality were collected both pre and post BMCs. In addition, compliance of the respective physicians to BMC decision was also calculated. SPSS version 20 was used for analysis. Descriptive statistics were performed. Results: Ninety-nine patients were discussed in this time period. The median age was 51 (range 17-68) years. The gender distribution was 70 males (70.7%) and 29 females (29.3%). Lung was the predominant site of malignancy (79, 79.8%). Thirty-one patients (31.3%) had EGFR TKI domain activating mutation, while 17 (17.2%) had anaplastic lymphoma kinase (ALK) rearrangement. The treatment plan was changed in 46 patients (46.5%). The intent of treatment was changed from palliative to curative in 5%. Change in the treatment plan with respect to surgery in 9.1%, radiation in 37.4%, chemotherapy in15.2%, targeted therapy in 22.9% and intrathecal in 6.1% patients, respectively. The compliance with the BMC decision in patients in whom it was changed was 84.8% (39, n = 46). Conclusion: Multidisciplinary management of difficult brain metastasis cases in specialised clinics has a significant impact on treatment decisions.
Background: Multiple low-cost biosimilars of bevacizumab are now available but their clinical efficacy has never been compared against the original (innovator) molecule in glioblastoma. The aim of the current analysis is to compare the overall survival (OS) in recurrent/progressive glioblastoma patients between the biosimilar and innovator molecules.Materials and methods: Adult recurrent/progressive glioblastoma patients treated with bevacizumab from 1 July 2015 to 30 July 2019 were identified. These patients were either offered Bevacizumab innovator (Avastin, Roche) or biosimilar (BevaciRel: Reliance Life sciences or Bryxta: Zydus Oncosciences) depending upon the financial status and affordability of the patients. The primary endpoint of the study was OS, while progression-free survival (PFS) and adverse events were the secondary endpoints.Results: There were 82 patients, out of which 57 received innovator and 25 received biosimilar bevacizumab. At median follow-up of 26 months, the median PFS was 3.66 (95% confidence interval (CI) 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and biosimilar group, respectively (Log-rank test p-value = 0.072). The hazard ratio (HR) for progression was 0.61 (95% CI 0.35 to 1.05; p-value = 0.075). At the time of data cutoff, the median OS was 5.53 (95% CI, 5.07 to 5.99) versus 7.33 months (95% CI, 5.63 to 9.03) in innovator and biosimilar group, respectively (Log-rank test p-value = 0.51). The HR for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). The adverse events and safety profiles were comparable between the two groups. Conclusion:In the recurrent/progressive glioblastoma patients, both innovator and biosimilar bevacizumab seem to have similar safety and clinical efficacy.
Background: Stress hyperglycemia is a common phenomenon in patients presenting with acute myocardial infarction (MI). We aim to evaluate the association of stress hyperglycemia at the time of hospital presentation and adverse cardiac events in myocardial infarction during the course of hospital stay. Methods: Subjects with age ≥18 years with acute MI were recruited on hospital admission and categorized based on admission blood glucose (<180 and ≥180 mg/dl, 50 patients in each group). Both groups were compared for clinical outcomes, adverse cardiac events and mortality. We also compared the adverse cardiac outcomes based on HbA1c levels (<6% and ≥6%). Results: Patients with high blood glucose on admission (stress hyperglycemia) had significant increased incidences of severe heart failure (Killip class 3 and 4), arrythmias, cardiogenic shock and mortality (p value = 0.001, 0.004, 0.044, and 0.008 respectively). There was no significant association between adverse cardiac events and HbA1c levels (heart failure 18.8% vs. 25%, p value = 0.609 and mortality 16.7% vs. 17.3%, p value = 0.856). Conclusions: Stress hyperglycemia is significantly associated with adverse clinical outcomes in patients with MI irrespective of previous diabetic history or glycemic control. Clinicians should be vigilant for admission blood glucose while treating MI patients.
NSCLC in the randomised Ph III IMpower150 study, including pts with EGFR or ALK genomic alterations. Here, we further analyse the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt) in this study. Methods: The 1202 enrolled pts received atezo (A) 1200 mg þ bev (B) 15 mg/kg þ carboplatin (C) AUC 6 þ paclitaxel (P) 200 mg/m 2 (ABCP) or A þ C þ P (ACP) or B þ C þ P (BCP) by IV q3w for 4 or 6 cycles per investigator (INV) decision, then q3w maintenance with atezo þ bev, atezo or bev, respectively. Co-primary endpoints were OS and INV-assessed PFS in the ITT-wild-type population (excluded pts with EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR mutations and pts with EGFR-mt disease who had prior TKI therapy.Results: These data represent 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt, including 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across the treatment arms were generally comparable to the ITT population. OS was improved with ABCP vs BCP in EGFR-mt pts, especially in pts with sensitising EGFR mutations (HR, 0.31 [95% CI: 0.11, 0.83]). This benefit extended to PFS (HR, 0.41 [95% CI: 0.23, 0.75]). See table for full efficacy results. Safety was similar between the EGFR-mt subgroup and the ITT population. Conclusions: IMpower150 is the first randomised Ph III trial of a checkpoint inhibitor to show a benefit in pretreated EGFR-mt pts. Adding atezo to standard-of-care bev and chemo provided survival benefit in EGFR-mt pts who have failed TKIs, for whom this regimen may represent a new treatment option.
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