PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study.

BACKGROUND: This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference trastuzumab (Herceptin®) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line treatment for HER2-positive metastatic breast cancer. METHODS: Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014 plus paclitaxel (PF-05280014 group; n = 352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n = 355). PF-05280014 or trastuzumab-EU was administered weekly (first dose 4 mg/kg, subsequent doses 2 mg/kg), with the option to change to a 3-weekly regimen (6 mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression. Paclitaxel (starting dose 80 mg/m2) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and confirmed by Week 33, based on blinded central radiology review. RESULTS: The risk ratio for ORR was 0.940 (95% CI: 0.842-1.049). The 95% CI fell within the pre-specified equivalence margin of 0.80-1.25. ORR was 62.5% (95% CI: 57.2-67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3-71.4%) in the trastuzumab-EU group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety outcomes and immunogenicity were similar between the treatment groups. CONCLUSION: When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01989676.

Cervical Cancer in SAARC Countries.

Purvish M. ParikhIn the year 2020, a total of 342 000 women were estimated to die of cervical cancer, of which 90%) were expected amongst low- and middle-income countries (LMIC). Globally incidence of cervical cancer has reduced as a result of improved personal hygiene, better living conditions and higher application of opportunistic screening programs. Yet GLOBOCAN shows that absolute number of cases are still increasing. We therefore conducted a 21 question multiple choice questionnaire online survey in Jan 2023 amongst 9 SAARC countries. A total of 367 replies were received and the representative answers for each country are being reported in this manuscript. A good possibility of achieving World Health Assembly target (Nov 17, 2020) was felt only by Bhutan and Nepal. For screening, most countries (Bhutan, India, Myanmar, Nepal, Pakistan and Sri Lanka) recommend for all asymptomatic eligible patients. Public health experts have suggested VIA / VILI as the best solution for LMICs. However, a dual screening strategy (HPV DNA plus) cytology was preferred by doctors in Afghanistan, Bhutan, India, Myanmar, Pakistan and Sri Lanka. Screening, triage and then treatment was the preferred by Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka. HPV vaccination was recommended in all girls between ages 10 to 26 years in Bangladesh, India, Myanmar, Nepal, Pakistan and Sri Lanka. All the 9 countries would use HPV vaccination to all eligible patients if the cost of the vaccine was reasonably low. Our survey clearly outlines challenges faced in tackling cervical cancer in SAARC countries. We also provide consensus regarding several potential solutions that can be used in both public and private cervical cancer control programs.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Rituximab biosimilar for the treatment of diffuse large B-cell lymphoma: a phase 3 randomized study in India.

PURPOSE: Very few studies have demonstrated the rituximab biosimilarity in terms of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity in patients with diffuse large B-cell lymphoma (DLBCL) in India. Therefore, we compared the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of our biosimilar rituximab with the reference rituximab (Ristova, Roche products [India] Pvt. Ltd) in patients with DLBCL in India. METHODS: A phase 3, randomized, assessor-blind, parallel-group, two-arm study was conducted across 28 sites in India. A total of 153 newly diagnosed DLBCL patients were randomized to receive either biosimilar rituximab or reference rituximab. The study drugs were administered at a dose of 375 mg/m2 by intravenous infusion every 3 weeks for six cycles. The primary end point was objective response rate (ORR) at the end of Cycle 6. Secondary end points included: pharmacokinetic, pharmacodynamics, immunogenicity, and safety assessment. RESULTS: The ORR at the end of Cycle 6 was 82.14% in the biosimilar rituximab and 85.71% in the reference rituximab group. The risk difference (90% CIs) was - 3.57 (- 14.80, 7.66). It met the non-inferiority margin of - 20%. The pharmacokinetic and pharmacodynamic parameters were comparable between the two treatment groups. The incidence rate of immunogenicity was very low and similar in both the treatment groups. The safety profile of both the treatments was comparable with no major difference in terms of nature, frequency and severity of TEAEs. CONCLUSION: The study demonstrated the biosimilarity between the biosimilar rituximab and the reference rituximab. Our biosimilar rituximab could add to the cost-effective treatment alternatives for patients with DLBCL in India.

Outcome of COVID-19 Infection in Cancer Patients in Pune.

Introduction We document our data on the course of the coronavirus disease 2019 (COVID-19) infection in cancer patients in an attempt to help optimize their management in India and globally. Material and Methods Between February 2020 and January 2021, participating oncologists from Pune (members of the Oncology Group of Pune) documented effect of COVID-19 infection in their cancer patients. Binomial logistic regression analysis as well as correlation analysis was done using Pearson Chi-square test to determine significance of clinical factors. Results A total of 29 oncologists from 20 hospitals contributed their data involving 147 cancer patients who developed COVID-19 infections. COVID-19 infection resulted in higher deaths (likelihood ratio of 4.4) amongst patients with hematological malignancies (12/44 = 27.2%) as compared with those with solid tumors (13/90 = 14.4%, p = 0.030). Patients with uncontrolled or progressive cancer (11/34 = 32.4%) when they got infected with COVID-19 had higher mortality as compared with patients whose cancer was under control (14/113 = 12.4%; p = 0.020). Complication of thromboembolic episodes (seen in eight patients; 5.4% cases) was associated with higher risk (25.6 times) of death (five-eighths; 62.5%) as compared with those who did not develop it (20/139;14.4%; p <0.001). Discussion Patients with cancer should be advised to take strict precautions to reduce the risk of being infected with COVID-19. They should also be given priority for COVID-19 vaccination. If infected with COVID-19, patients with hematological malignancy and uncontrolled cancer are at higher risk of morbidity and mortality. When they are being treated (OPD or inpatient basis), additional precautions are necessary to ensure their exposure to potential COVID-19 virus is minimized. If they get infected with COVID-19, they should be given aggressive treatment to prevent complications, especially thromboembolic episodes. If they develop any thromboembolic complication, their risk of dying are significantly higher, and management should be modified accordingly.

An Ayurveda Gargle Regimen in Management of Radiotherapy-induced Oral Mucositis.

Background Radiotherapy-induced oral mucositis (RIOM) in patients with head and neck cancer may lead to significant morbidity. OM may result in erythema, ulceration, and pseudomembrane formation. The usual time of onset is second or third week of radiotherapy (RT), after the doses of 16 to 18 Gy. OM may cause severe pain, significant weight loss, increased resource use, interruption or discontinuation of the treatment, and added cost of supportive care. Materials and Methods Patients who underwent RT and chemoradiation (CTRT) for head and neck squamous cell carcinoma (HNSCC) from 2015 to 2016 were included. The patients who were treated with the add-on Ayurveda gargle regimen (AGR) of sapthachhadadi gandoosham were evaluated against patients treated with standard symptomatic care (SSC). Statistical Analysis Chi-square test was used to compare the difference between the two groups in the present study with SPSS (SPSS version 20 for Windows package SPSS Science, Chicago, IL, USA). software. Result Grade III to IV OM was lower in the AGR group when compared with the SSC group ( p < 0.001). Onset of OM was significantly delayed in patients from the AGR group ( p < 0.001). Conclusion The AGR with sapthachhadadi gandoosham is effective in delaying the onset and reducing severity of OM in HNSCC, without compromising the rate of locoregional recurrence.

Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit.

INTRODUCTION: Anemia is a common, underestimated problem in cancer patients receiving myelosuppressive chemotherapy and has significant adverse effect on the quality of life and outcome. Darbepoetin has been shown to be effective in this setting, but controversy surrounds it actual use. METHODS: We analyzed prospectively collected clinical practice data of patients receiving darbepoetin in a real-world setting for this retrospective audit. Patients with baseline hemoglobin (Hb) of <11 g/dl were included in this analysis. Their medical records were audited using a predetermined 35-point pro forma. RESULTS: There were a total of 274 patients with advanced cancer receiving myelosuppressive chemotherapy who had baseline Hb <11 g/dl and who were given darbepoetin. Head-and-neck squamous cell carcinoma, lung cancer, and breast cancer were the most common cancers. Their median baseline Hb was 8.9 g/dl which rose to 11.2 g/dl at the end of commenced therapy, along with improved symptomatology. There were no new toxicities, and only two patients required discontinuation of darbepoetin due to toxicity. CONCLUSION: Darbepoetin is safe and effective in the prevention and management of anemia among patients receiving myelosuppressive chemotherapy.

First-line management of metastatic non-small cell lung cancer: An Indian perspective.

Lung cancer has been the most common cancer in the world for several decades. The non-small cell lung cancer (NSCLC) constitutes approximately about 80% of the total cases of lung cancer. Therapeutic interventions in NSCLC have shifted to the target-based approach from histology-based approach, and this has completely changed the face of the management of NSCLC. Developing countries, such as India, have very limited data compiled about the prevalence and treatment practices of lung cancer, despite a large burden of the disease. However, in recent times, there has been a lot of data generated in this regard. This article is an attempt to collate and shine light on the available data for the first-line treatment of NSCLC in India keeping in mind the current standards of care in this area.

Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer.

BACKGROUND: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. METHODS AND MATERIAL: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. RESULTS: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months).

Survey of Implementation of Antiemetic Prescription Standards in Indian Oncology Practices and Its Adherence to the American Society of Clinical Oncology Antiemetic Clinical Guideline.

PURPOSE: Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. METHODS: This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. RESULTS: Sixty-six (62.9%) of 105 responded and 65 centers (98.5%) were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8%) than the highly emetogenic regimens (6.1%). The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%), lack of national guidelines (12 centers; 18.2%), and lack of administrative support (10 centers; 15.2%). CONCLUSION: Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice.

Indian data on bone and soft tissue sarcomas: A summary of published study results.

Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with osteosarcoma (OGS), chondrosarcoma, and Ewing sarcoma being the most common cancers in this subset. The formation of disease management groups/clinics focused on sarcomas has resulted in better understanding and management of these uncommon tumors. Multiple large-scale retrospective data from Tata Memorial Hospital (TMH) and All India Institute of Medical Sciences have reported outcomes comparable to Western data in the field of OGS and Ewing sarcoma, with interesting prognostic factors identified for further evaluation. Soft tissue sarcomas are a rare heterogeneous group of tumors, more than 50 different tumor entities. The common subtypes identified in India include Ewing sarcoma and synovial sarcoma. Valuable work regarding brachytherapy has been done by radiation oncologists from the TMH, especially in pediatric patients.

Breast cancer: An overview of published Indian data.

The Incidence of breast cancer has been steadily increasing in the last two decades, more so in urban areas of the sub-continent. Cancer ceters across the country have large numbers of patients being treated with multiple publications in this field. Inspite of paucity of prospective data and randomised clinical trials from India, there are large number of retrospective publications on various aspects of the disease including pathology, radiology, surgery, chemotherapy, radiation, palliative care and alternatitive treatment modalities. These published data provide an insight into the trends of breast cancer in the country and this comprehensive data review of Indian data will provide a basis for designing trials relevant to our population and planning health care.

Open-label observational study to assess the efficacy and safety of aprepitant for chemotherapy-induced nausea and vomiting prophylaxis in Indian patients receiving chemotherapy with highly emetogenic chemotherapy/moderately emetogenic chemotherapy regimens.

CONTEXT: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian population with aprepitant containing regimens. AIMS: The aim was to assess the Efficacy and Safety of Aprepitant for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy/moderately emetogenic chemotherapy (HEC/MEC) regimens. SETTINGS AND DESIGN: Investigator initiated, multicentric, open-label, prospective, noncomparative, observational trial. SUBJECTS AND METHODS: Triple drug regimen with aprepitant, palonosetron, and dexamethasaone administration was assessed for the prevention of CINV during acute, delayed, and the overall phase (OP) for HEC/MEC Regimens. The primary endpoint was complete response (CR; no emesis and no use of rescue medication) and the key secondary endpoint was the complete control (CC; no emesis, no rescue medication and no more than mild nausea) during the OP. STATISTICAL ANALYSIS USED: Perprotocol efficacy was analyzed for the first cycle with results represented in terms of CR/CC rates using descriptive statistics. RESULTS: Seventy-five patients were included in the study with median age of 49.7 years and 89.7% being females. The CR rate (OP) for patients administered HEC or MEC regimens during the first cycle were 92% and 90.9%, respectively. Similarly, the CC rates (OP) were 75% and 90% for these regimens, respectively. 7 (9.2%) patients reported adverse drug reactions that were mild and transient with no reports of any serious adverse events. CONCLUSIONS: Use of aprepitant containing regimen for patients receiving HEC/MEC regimen resulted in significantly high CR and CC response rates, which further consolidate its potential role to improve patient quality of life and compliance to disease management.

Tolvaptan.

Hyponatremia is a common and often under-recogonised clinical problem in oncologic practice. The recogonition of the cause of hyponatremia and initiation of appropriate and timely intervention can prevent morbidity and improve treatment tolerance. This drug review aims at discussing the currently approved oral vaptanagent Tolvaptan. Vaptans including Tolvaptan act as "aquaretic" agents cousing excretion of water while retaining the sodium. Administration of this agent for prescribed periods result in improvement of serum sodium levels. The drug can be used in many clinical situations resulting in hyponatremia including congestive heart failure, cirrhosis and syndrome of inappropriate ADH secretion (SIADH) including SIADH related to malignancies.

Importance of dose intensity in treatment of advanced non-small cell lung cancer in the elderly.

Maintaining appropriate dose intensity is important not only in the curative setting but also in treatment with palliative intent. We evaluated the outcome of advanced non small cell lung cancer treated with doublet platinum based chemotherapy. Outcome was compared between patients treated by medical oncologists at a tertiary cancer center and those treated by non medical oncologists in the community. The dose intensity, overall response rate and overall survival was significantly better when patients were treated by trained qualified and experienced medical oncologists. Hence, even in the palliative setting, cancer directed systemic therapy will yield maximum benefit for the patients when treated by medical oncologists.