A Randomized, Double-Blind, Phase III Study in India for Comparing Efficacy, Safety, and PK of ZRC-3277 (Pertuzumab Biosimilar) With Perjeta® in Patients With HER2-Positive Metastatic Breast Cancer.

INTRODUCTION: To evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups. RESULTS: In the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (-12.19%, 3.11%) for the difference in ORR (-4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups. CONCLUSION: Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

Efficacy and Safety of BP02 (Trastuzumab Biosimilar) in HER2-Positive Metastatic Breast Cancer: A Multicenter Phase III Study.

BACKGROUND AND OBJECTIVE: Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02, a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as a trastuzumab biosimilar. The objective of this study was to evaluate the equivalence of BP02 with reference trastuzumab (RT: Herceptin®-EU) in patients with HER2-positive metastatic breast cancer. METHODS: This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75 mg/m2 on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. RESULTS: Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ± 13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively. CONCLUSIONS: BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks. CLINICAL TRIAL REGISTRATION: CTRI Number: CTRI/2020/04/024456.

Clinico-demographic Profile of Carcinoma Urinary Bladder-5-Year Experience from a Tertiary Care Centre of Eastern India.

Urinary bladder carcinoma is a disease of the elderly and often presents at an advanced stage due to ignorance and manifestation of symptoms at later stages of the disease. In India, very little data is available regarding the clinico-epidemiological pattern of urinary bladder cancers. In this study, we analysed the clinico-demographic profile of patients with urinary bladder carcinoma, attending a tertiary care centre in Eastern India over the last 5 years. We analysed the database of Oncology OPD of a tertiary care centre in West Bengal in Eastern India and collected the demographic, clinical and treatment data of urinary bladder carcinoma patients who attended our OPD between 2017 and 2021. The objective was to assess the demographic and clinical profile of these patients and compare them with those reported from other parts of India as well as the rest of the world. Majority of patients (70%) were above 50 years of age with a strikingly huge male predominance (male:female = 6.6:1). Transitional cell carcinoma (TCC) was the most common (90%) histology. 67.2% of the cases were muscle-invasive disease at presentation, and 19.3% of the patients presented with metastatic disease with bone (42%) as the most common site of metastasis. Overall, around 22% of patients underwent surgery either with definitive or palliative intent. Sixty-five percent of the patients who received radiotherapy underwent definitive radiation as a part of bladder preservation protocol. Thirty-five percent of all patients received chemotherapy; most of them (50.5%) received chemotherapy as neoadjuvant treatment before definitive therapy. To conclude, it can be said that this study is one of its first from Eastern India and will act as a stepping stone for future studies concentrating on clinico-epidemiological profile, early diagnosis and treatment of carcinoma urinary bladder.

Clinico-Demographic Profile Of Soft Tissue Sarcoma- 5 Year Experience From A Tertiary Care Centre Of Eastern India.

Soft tissue sarcomas (STS) are a diverse group of malignant mesenchymal neoplasm.But, due to their low prevalence, very little data is available worldwide as well as in India regarding their clinico-epidemiological pattern.In this study we analysed the clinico-demographic profile of STS patients attending a tertiary care centre of Eastern India over the last 5 years. We analyzed the prospectively maintained database of a tertiary care centre of West Bengal in Eastern India, and collected the data regarding the demography, clinical profile, pathology and treatment of STS patients who attended our OPD between 2017-2021. The objective was to assess the demographic and clinical data of STS patients of Eastern India and compare it with those of the reported literature from rest of the country as well as outside world. Most of the cases (27%) were between 41-50 years of age group with a slight male predominance (Male: Female = 1.01:1). Spindle cell sarcoma was the most common (24.3%) histology followed by undifferentiated pleomorphic sarcoma (15%) and extremities were the most common site of involvement (47.7%). 71% patients presented with stage III and advanced disease.81% patients underwent radical surgery,14% patient received neo-adjuvant and 60% received adjuvant radiotherapy.91% patients received systemic chemotherapy. To conclude, this study is one of its first from Eastern India and will act as a stepping stone for future studies concentrating on clinico-epidemiological profile, early diagnosis and treatment of STS.

Neoadjuvant chemotherapy for locally advanced head and neck squamous cell carcinoma - Is it still relevant? A practice pattern survey among oncologists of India.

Objectives: Concurrent chemotherapy is the recommended treatment for locally advanced head and neck (H&N) squamous cell carcinoma, and neoadjuvant chemotherapy (NACT) is debated with a few special indications. NACT for advanced head and neck cancer has been studied in clinical trials for more than 2 decades without clear demonstration of the benefit for loco regional tumor control or overall patient survival. Its benefit remains controversial in the absence of clear evidence to define its role. However, there is widespread use of NACT among oncologists. We conducted an online survey to find out the frequency, pattern, prevalence, and aims for use of NACT in locally advanced head and neck cancers among radiation, medical, and surgical oncologists. Materials and Methods: Oncologists across India who expressed interest to participate in our survey were asked to complete a short online questionnaire designed to identify the current practice pattern of NACT in head and neck cancer. A mobile app-based questionnaire was sent to 200 oncologists across the country to assess the pattern of NACT use and to solicit their most frequent therapy approach for patients with locoregionally advanced head and neck cancer. Results: One hundred and fifty (150) oncologists completed and returned the survey (75%), and 130 were finalized (94 radiation oncologists, 19 medical oncologists, and 17 surgical oncologists). The single most common treatment approach reported for patients with locoregionally advanced H&N cancer was that of sequential chemoradiation (61%), specifically NACT with the TPF regimen (78.5%), followed by radiation therapy. The primary objectives cited by respondents for the use of NACT included the desire to buy time for definitive treatment (20%) and to achieve R0 resection (19.2%). Use of NACT in most patients was more preferred by medical oncologists (21.1%) and radiation oncologists (19.1%) than surgical oncologists (11.8%). Thus, there is not much difference in perception in practice of NACT in radiation, medical, and surgical oncologists. A minimum of two cycles of NACT was preferred by more than half of the doctors (55.4%) with 59.6% radiation oncologists using it before further assessment. Conclusion: Although level I evidence for inferior outcomes with NACT as compared to concurrent chemoradiation therapy is there, the use of NACT is quite common among various oncologists in the country because of reasons such as buying time for definitive treatment, achieving R0 resection, better outcome and survival, partial response, better tolerability, better distant control, LN size regression, down-staging of primary tumor, selection of chemosensitive patients, reducing the volume of the radiation field, and better tolerability of subsequent Chemoradiation (CTRT) intensity of subsequent chemoradiation therapy.

A comparative study of duration of postoperative analgesia between epidural bupivacaine and epidural clonidine plus bupivacaine in lumbar laminectomy surgery under general anaesthesia.

A randomised prospective double-blind placebo controlled study was undertaken in 60 patients of ASA-I and II, scheduled for lumbar laminectomy under general anaesthesia using thiopentone, fentanyl, artracurium, N2O/O2 and isoflurane. After obtaining written Informed consent from all patients, they were randomly allocated to two equal groups ie, group A (n = 30) and group B (n = 30). Group A patients received clonidine 0.5 ml (75 microg) plus 5 ml 0.25% bupivacaine and group B patients received 5 ml 0.25% bupivacaine plus 0.5 ml of normal saline (NS) as a control through epidural route placed by the surgeon at the closure of the surgery. All the vital parameters were recorded at the time of epidural catheter placement and administering drugs and at 10 minutes interval thereafter till the patients were reversed with neostigmine and glycopyrrolate and then in the postanaesthetic care unit (PACU) at 15 minutes interval till the end of the study. All patients received injection diclofenac 75 mg IM as soon as they complained of pain or when the VAS score became > or = 4cm. The study ended when patients received injection diclofenac 75 mg IM as rescue analgesic. Any feature of motor block, sedation score and event of urinary retention were recorded in the PACU. Duration of postoperative analgesia was taken as the primary outcome and measured from the time of regaining full consciousness following surgery till receiving first injection of rescue analgesic in the PACU. Duration of postoperative analgesia was (546.36 +/- 11.55 minutes) in group A compared to (240.15 +/- 07.32 minutes) in group B. No clinically significant difference was found in heart rate, blood pressure, respiratory rate, oxygen saturation and motor blockade. Sedation score was slightly higher in group A, which was not significant. So small dose of clonidine (75 microg) as an adjuvant to 5 ml 0.25% bupivacaine in epidural route following lumbar laminectomy significantly prolonged postoperative analgesia and improved patient satisfaction without any clinically significant adverse reaction.

Clinicopathologic profile of non-Hodgkin's lymphoma in a rural medical college.

A prospective study was done at North Bengal Medical College, Sushrutanagar, Darjeeling, West Bengal over a period of two years. All patients diagnosed as non-Hodgkin's lymphoma were analysed for clinical presentation, classified according to the Working Formulation and staged according to Ann Arbor staging system. A lower median age (39.94 years) of onset and higher male to female ratio (3.22:1) as compared to western countries were observed. We found neck swelling was the commonest presenting symptom (65.79%) and peripheral lymphadenopathy was the commonest sign (94.74%). "B symptoms" were noted in 63.16% cases. Cervical lymph nodes were commonly involved (78.95%), followed by axillary (55.26%). Thoracic lymph nodes were enlarged in 31.58% cases and abdominal lymph nodes in 18.42% cases. We found diffuse mixed variant was the commonest (31.58%) followed by diffuse large cell (18.42%). At presentation most of the cases were of intermediate grade (55.26%) and in stage III (44.74%). We conclude that there is a distinct geographical pattern of non-Hodgkin's lymphoma in respect of age, sex, grade and stage of the disease which is distinctly different from those of western countries.