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.

Elective Surgical Experience During COVID Pandemic at a Tertiary Cancer Care Centre in India: A Retrospective Analysis.

To analyse and identify possible outcomes of elective cancer surgeries performed at a tertiary cancer centre during COVID19 pandemic. This is a retrospective study including patients that underwent surgery at HCG Manavata cancer centre, Nashik, Maharashtra, India, from 15 March 2020 to 15 June 2020. Among the 458 patients that underwent elective surgeries, 54% were male and 46% were female, with a median age of 50.57 years. The most common sites of cancer distribution were head and neck (24.67%), colorectal (11.57%), gynaecological (11.35%), and breast (10.26%). Of the included patients, 92% were of American Society of Anaesthesiologists (ASA) II with comorbidities such as hypertension, and 64% underwent major surgeries with a mortality rate of 1.52% (n = 7). Average duration of surgery and hospital stay was observed to be 168.43 min and 4.4 days, respectively. Post-operatively, 7 patients were tested COVID positive and their recovery was uneventful. Despite the difficulty that set in because of COVID19 pandemic, it was proven from our study that elective cancer care surgeries can be successfully performed by following all the set guidelines.

Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES.

BACKGROUND: This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC). METHODS: The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 - ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally. RESULTS: A total of 235 patients received ≥ 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥ 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained. CONCLUSION: The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 - ABC in Asian region.

Metachronous pleuropulmonary blastoma in an adult patient with endometrial cancer: a case report.

Pulmonary blastoma is a rare form of lung cancer with a reported incidence of 0.25-0.55 of primary pulmonary cancers. Pleuropulmonary blastoma (PPB) is a common finding in children while it is rarely found in adults. In the past few years, the incidence of a second primary tumour has increased to 3.5% followed by third primary tumour at 0.5% and fourth tumour at 0.3%. The clinical significance of diagnosing and distinguishing a secondary primary tumour is often challenging. As per our knowledge, this is the first case of metachronous PPB in an adult patient previously diagnosed with endometrial cancer.

A case report of high-grade astroblastoma in a young adult.

Astroblastoma is an uncommon neuroepithelial primary tumor of the brain which is of uncertain origin. We present a case of high-grade astroblastoma in an 18-year-old female with a severe headache, loss of appetite, vomiting and generalized weakness. The patient had undergone a right frontoparietal craniotomy. Large subfalcine meningioma was excised. The lesion was suspected to be a meningioma. Primary radiological investigation revealed a 6.8 cm × 5.8 cm × 5.4 cm lesion. Although the radiological and intraoperative findings were of an extra-axial tumor, the histology and immunophenotype was of an astroblastoma. The patient was treated with cyclophosphamide, cisplatin and etoposide chemotherapy regimen. The patient was later treated with bi-weekly bevacizumab. The patient had improved symptomatically post-chemotherapy. However, there was no significant difference in lesion size. The patient died after 2 weeks. The prognosis of patients with astroblastoma is extremely poor as observed in our case.