Comparison of Efficacy and Safety of a Bevacizumab Biosimilar, in Combination with Chemotherapies, in Nonresectable Metastatic Colorectal Cancer and in Advanced Nonsquamous Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study.

Ranjith K.The objective of this study was to compare the efficacy, safety, pharmacokinetics, and immunogenicity of a proposed bevacizumab biosimilar (DRL_BZ) with the innovator Avastin (reference medicinal product [RMP]) in patients with nonresectable metastatic colorectal cancer (mCRC) over a period of 9 months and advanced nonsquamous non-small cell lung cancer (NSCLC) over 6 months. The study was planned as a randomized, double-blind trial. In part A, a total of 117 mCRC patients were intended to receive 5 mg/kg of bevacizumab every 2 weeks along with mFOLFOX6 chemotherapy for a maximum of 18 cycles. In part B, 60 NSCLC patients were to receive 15 mg/kg of bevacizumab every 3 weeks along with pemetrexed and carboplatin for the initial four cycles, followed by pemetrexed for another four cycles. The primary endpoint was the progression-free survival rate at 6 months (PFS6) in both subparts. The anticipated sample size was 106 evaluable mCRC patients to achieve 85% statistical power for concluding noninferiority with a margin of half the difference (18.8%) between DRL_BZ and Avastin, along with a pilot study involving 60 evaluable NSCLC patients. Safety comparison included assessing adverse events (AEs), infusion reactions, and lab abnormalities. Immunogenicity comparison involved the incidence of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs). Pharmacokinetic comparison was planned after the first and fourth dosing cycles of treatment in 24 NSCLC patients. The PFS6 for mCRC patients treated with DRL_BZ and RMP was 57.8% and 50% respectively, with a difference in efficacy of 7.8 (-8.7, 23.7). The PFS9 was 31.1% and 22.9%, with a difference of 8.2% (-6.9%, 22.9%). The objective response rate (ORR) for DRL_BZ and RMP was 28.8% and 22.4%, while the disease control rate (DCR) was 44.2% and 37.9% respectively. For NSCLC patients, the PFS6 was 44% and 45%, showing a difference of -1.0 (-4.2, 22.1). The ORR was 41.4% and 48.1%, and the DCR was 62.1% and 63%. The frequency, type, and severity of AEs were similar in both indications. Blood levels during the first and fourth dosing cycles exhibited comparable values. All NSCLC patients tested negative for ADA, while no mCRC patients on DRL_BZ tested positive for ADA. Low incidences of ADA (8%) and NAbs (4.0%) were reported in patients on RMP. Overall, the efficacy, safety, immunogenicity, and pharmacokinetic parameters of DRL_BZ and RMP were found to be comparable. Clinical Trial Registration For BZ-01-002: CTRI/2016/01/006481.

Efficacy, Safety, Pharmacokinetics, and Immunogenicity of DRL-Trastuzumab Versus Herceptin in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Randomized Controlled Trial.

PURPOSE: Dr Reddy's Laboratories Trastuzumab (DRL_TZ) is a biosimilar to Herceptin under development. The present study was conducted to evaluate efficacy, safety, pharmacokinetics (PKs), and immunogenicity of DRL_TZ in comparison with the reference medicinal product (RMP) along with concomitant weekly paclitaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). METHODS: This was a randomized, double-blind study in female patients with HER2-positive MBC, randomly assigned in a 1:1 ratio to receive either DRL_TZ or the RMP, that is, an innovator product sourced from the European region, along with additional chemotherapy, as first-line treatment for up to 24 weeks. The primary end point was the best overall response rate (ORR) as per RECIST 1.1 criteria. Progression-free survival rate at 6 months (PFS6), safety, immunogenicity, and PK parameters were assessed as secondary end points. RESULTS: A total of 164 patients were randomly assigned to receive either DRL_TZ or the RMP. Best ORR in the per-protocol population was comparable, 91.9% (93.3% CI, 83.2 to 96.3) versus 82.1% (93.3% CI, 72.0 to 89.1) in DRL_TZ and RMP arms, respectively; the difference between the arms was 9.8% with a 93.3% CI of -1.3 to 20.8. The PFS6 rate, safety, PK profile, and antidrug antibody incidence were comparable. An additional 44 patients were recruited in the postrandomization phase, in an open-label manner, and started on DRL_TZ to generate more data on efficacy, safety, and immunogenicity. The additional data with DRL_TZ, when pooled, were similar to the RMP data. CONCLUSION: DRL_TZ was found to have similar efficacy and comparable safety, PK, and immunogenicity profiles as the RMP.

Palliative radiotherapy and quality of life in patients with locally advanced thoracic esophageal cancer: a single centre experience from Central India.

Background: Patients with locally advanced esophageal squamous cell carcinoma (LAESCC ) have decreased quality of life (QoL) and, thus, require palliative external beam radiotherapy (EBRT). The present study was performed to evaluate the QoL in patients with LAESCC undergoing palliative EBRT. Materials and methods: This was a prospective, observational study performed over a period of 18 months (from December 2018 to May 2020) in the Department of Radiation Oncology. Seventy patients with LAESCC received EBRT (30 Gy in 10 fractions, at 3 Gy per fraction over 2 weeks). Patients were followed-up at monthly intervals for 3 months. The dysphagia and odynophagia scores were calculated at baseline and follow-up visits. The QoL was assessed with 18-item EORTC QLQ-OES questionnaire at baseline and 3 months. Results: Over the study period, significant decrease in mean dysphagia and odynophagia score was observed (p-value < 0.0001). On post-hoc analysis, significant decrease in both dysphagia and odynophagia score was observed between baseline and at the end of study and between various follow-up visits (p-value < 0.0001). Moreover, there was a significant increase in mean body weight (p-value < 0.0001). At 3 months, there was a significant decrease in dysphagia (p-value < 0.0001), eating (p-value < 0.0001), reflux (p-value = 0.005), pain (p-value < 0.0001), and saliva (p-value = 0.01) domains of EORTC QLQ-OES18 questionnaire. Conclusion: In patients with LAESCC, EBRT leads to significant decrease in dysphagia and odynophagia, and increase in body weight. These changes indirectly lead to improved QoL.

A study to evaluate resource draining "no shows".

INTRODUCTION: Waiting lists are problems that plague all government radiation therapy centers across the country, leading to disease progression, and reduced treatment efficacy. No shows for appointments create artificial access issues, reduce revenues, waste staff time, and negatively affect patient care. METHODOLOGY: A Retrospective analysis of 180 patients, who were given an appointment and were to be started for radiation therapy at the Department of Radiation Therapy and Oncology, at our institute from May 1, 2013 to July 31, 2013, was done. Patients were divided into two Groups; Group A (n = 104, 57.8%) that complied for treatment and Group B (n = 76, 42.2%) that did not comply for treatment on the scheduled date. The Group B ("no shows") patients were contacted telephonically and were evaluated for the primary reasons for their failure to comply for treatment through a preformed questionnaire. RESULTS: The mean age, gender distribution and patient's habitat in both the groups were comparable. On Group B analysis, the average waiting period for the appointment was 74 days; 31.4% had died within an average of 31 days; 37.1% said they were better; 10% said their condition was the same; 18.6% said their disease had progressed. Patients were also evaluated for various factors responsible for their not reporting for treatment at the institute. CONCLUSION: Better communication and constant reminders between patients and the departmental staff can go a long way in helping to curb the problem of no shows and mitigate the artificial access issues. This would lead to better patient care and better resource utilization.

Conventional vs concomitant boost radiotherapy with concurrent cisplatin in advanced head and neck cancer.

AIM OF STUDY: To compare outcome of concomitant boost therapy (CBT) with conventional radiotherapy with cisplatin as a radiosensitizer in advanced head and neck cancer. SUBJECTS AND METHODS: Prospective comparative study was undertaken. Patients were assigned alternately to ArmA (conventional arm) and ArmB (CBT arm), 30 in each arm and total 60 patients were enrolled. RESULTS: Out of 30 patients in conventional Arm A, 13 had complete response (CR; 43.33%), 9 had partial response (PR; 30%), three patients (10%) had stable disease (SD), and five patients (16.66%) had progressive disease (PD). In arm B out of 30 patients, 18 patients (60%) had CR, five patients (16.66%) had partial response (PR), four patients (13.33%) showed SD, and three patients (10%) had PD. There was no statistically significant difference between the two arms for CR (P - value = 0.196). CONCLUSIONS: CBT can be used as an alternative to conventional RT in advanced head and neck cancers which minimize the total duration and the workload can be reduced. The locoregional control with CBT is comparable with the response of conventional RT.