The clinical utility and safety of short-course immune checkpoint inhibitors in multiple tumours-A real-world multicentric study from India.

The real-world data on short course of immune checkpoint inhibitor (ICI) use are sparse and merit exploration. A multicentric observational study on the safety and efficacy of ICI in oncology patients between August 2014 and October 2020 involves 1011 patients across 13 centers in India. The median age was 59 (min 16-max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles was 5 (95% confidence interval [CI] 1-27), and the median duration of therapy was 3 (95% CI 0.5-13) months. ICIs were used commonly in the second and third line setting in our study (66.4%, n = 671). Objective response rate (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease, and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n = 906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow-up of 14.1 (95% CI 12.9-15.3) months, there were 616 events of progression and 443 events of death, and the median progression free survival and overall survival were 6.4 (95% CI 5.5-7.3) and 13.6 (95% CI 11.6-15.7) months, respectively, in the overall cohort. Among the immune-related adverse events, autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy have comparable efficacy/safety to international literature with standard ICI therapy.

An observational single-center study of nivolumab in Indian patients with recurrent advanced non-small cell lung cancer.

PURPOSE: Limited treatment options are available for patients with advanced non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. The treatment of recurrent advanced NSCLC progressed with the arrival of nivolumab and other immunotherapeutic agents. Our single-center prospective study aimed to present the effectiveness and safety of nivolumab in second-line setting after first-line platinum doublet in Indian patients with advanced NSCLC. PATIENTS AND METHODS: Twenty-nine adult patients with stage IV NSCLC treated with nivolumab after failure of first-line platinum-based chemotherapy at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, India, between October 2016 and January 2018, were included in the study. Overall survival (OS), hematological, and nonhematological toxicities were evaluated. RESULTS: A total of 29 patients (mean age of 59.6 years at enrollment) were evaluated. Histological evaluation revealed adenocarcinoma (44.8%) and squamous (55.2%) type of cancer. The Eastern Cooperative Oncology Group performance score was II in 7 patients (24.1%) and I in 22 (75.9%) patients. Patients received an average of four cycles of nivolumab. The median survival duration was 101 days, and OS rate in the study was 51.7%. Six patients (20.7%) had stable disease response, five patients (17.2%) had partial response, and three patients (10.3%) were lost to follow-up. Asthenia and cough were the most common nonhematological toxicities. Only three patients developed hematological toxicities (anemia and thrombocytopenia). CONCLUSION: Data from our study suggest nivolumab is well-tolerated and effective in Indian patients with recurrent advanced NSCLC after failure of the multiple first lines of platinum-based combination chemotherapy.

Prostate Carcinoma and Pleural Mesothelioma: An Extremely Rare Co-occurrence.

Pleural mesothelioma and carcinoma prostate as metachronous double malignancy is extremely rare co-occurrence. A 67-year-old male, diagnosed case of carcinoma prostate with bone metastasis, was treated with chemotherapy and hormone therapy. He responded well to chemotherapy and hormone therapy. He remained asymptomatic for two years with serum prostate-specific antigen (PSA) values within normal limits. After two years of diagnosis of carcinoma prostate, he developed left lung pleural sarcomatoid mesothelioma as a second metachronous tumor. Malignant pleural mesothelioma as a metachronous second tumor in a case of carcinoma prostate is rarely reported in the literature. The long-life expectancy, old age, late effects of the treatment, genetic predisposition and lifestyle factors of patients with carcinoma prostate expose them to the possibility of developing second primary tumor.

Efficacy of erlotinib as first-line maintenance therapy in patients with locally advanced or metastatic nonsmall cell lung cancer who have not experienced disease progression or unacceptable toxicity during chemotherapy.

BACKGROUND: First-line maintenance with erlotinib in nonsmall cell lung cancer (NSCLC) patients without progression after four cycles of chemotherapy was well tolerated and significantly prolonged progression-free survival (PFS) compared with placebo. AIM AND DESIGN: This open-label, single arm, Phase IV, interventional study was designed to evaluate erlotinib as first-line maintenance after chemotherapy in Indian NSCLC patients. Primary efficacy objective was to evaluate PFS rate (PFSR) at week 52 and secondary objectives were determination of PFS, overall survival (OS), overall response rate (ORR), disease control rate, and safety. SUBJECTS AND METHODS: Patients were treated with erlotinib until disease progression/death/unacceptable toxicity or end of study. Patients with disease progression underwent scheduled clinical assessments every 12 weeks thereafter. Kaplan-Meier estimates were used to evaluate PFSR, PFS, and OS. The ORR was summarized using number and percentage along with two-sided 95% Clopper-Pearson confidence interval. The incidence of adverse events (AEs) and serious AEs (SAEs) was tabulated according to severity, outcome, and relationship to erlotinib. RESULTS: Of the 51 enrolled patients, 47 patients completed the study (2: Continuing treatment, 41: Disease progression, and 4: Death) and four patients discontinued treatment (3: Lost to follow-up; 1: Withdrew consent). PFSR was 22.5% at 12 months, median PFS 99 days (14.14 weeks), and median OS was 671 days (22 months). The probability of OS was 74.5% at 14 months. The ORR was 25.5%, and disease control rate was 55.3%. AEs were reported in 62.7% and SAE in 7.8% of patients. Common AEs were diarrhea and rash. CONCLUSIONS: Erlotinib was well tolerated by Indian patients in first-line maintenance setting and resulted in median PFS of 14 weeks and median OS of 22 months better than previously reported and with no new safety concerns in this population.

Myelodysplastic syndromes: a challenging disease for patients and physicians.

The biological mechanisms underlying the ineffective haematopoiesis and increased risk of leukaemic evolution in MDS is largely known. A careful clinical and cytogenetical assessment is required to correctly classify and risk stratify the patients. A curative approach with allogeneic stem cell transplantation should always be considered at the initial assessment. In low-risk patient receiving chronic RBC transfusions, symptomatic iron-overload is a reality and carries a significant mortality, and therefore, the iron status should be monitored and chelators used when indicated. The first line treatment of anaemia is erythroid growth factors. Lenalidomide is a highly potent therapy in low-risk MDS with del 5q, however, the treatment carries a high risk of rapidly developing neutropenia and thrombocytopenia. Several promising drugs are currently under investigation in low-risk MDS including thrombopoietin analogues and epigenetically active drugs.

Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study.

BACKGROUND: Targeting of VEGF is a potential therapeutic option in patients with malignant ovarian ascites. We present the final results of a multicentre study of the efficacy and safety of aflibercept, a potent inhibitor of both VEGF and placental growth factor, in the treatment of malignant ascites. METHODS: In this double-blind, placebo-controlled, parallel-group, phase 2 study, patients with advanced chemoresistant ovarian cancer and recurrent symptomatic malignant ascites were randomly assigned (1:1) via an interactive voice response system to either intravenous aflibercept (4 mg/kg every 2 weeks) or placebo, stratified by interval of time (≤ 2 weeks vs > 2 weeks) between the two most recent paracenteses before randomisation. Patients participated in the double-blind period (during which patients, investigators, and sponsor personnel were masked to treatment assignment) until they had a repeat paracentesis and for at least 60 days, and could also participate in an optional open-label period during which all patients received aflibercept. The primary efficacy endpoint was time to repeat paracentesis based on response during the double-blind period alone, and was analysed in the intention-to-treat population with censoring of patients who did not have a repeat paracentesis as of the last day of the double-blind period. Safety analyses included both double-blind and open-label periods. This study is registered at ClinicalTrials.gov, number NCT00327444. FINDINGS: 55 patients with a median of four (range two to 11) previous lines of chemotherapy were randomly assigned to receive placebo (n=26) or aflibercept (n=29). Mean time to repeat paracentesis was significantly longer with aflibercept than with placebo (55·1 [SE 7·3] vs 23·3 [7·7] days; difference 31·8 days, 95% CI 10·6-53·1; p=0·0019). In the aflibercept group, two patients did not need a repeat paracentesis during 6 months of double-blind treatment. The most common grade 3 or 4 treatment-emergent adverse events were dyspnoea (six [20%] aflibercept vs two [8%] placebo), fatigue or asthenia (four [13%] vs 11 [44%]), and dehydration (three [10%] vs three [12%]). The frequency of fatal gastrointestinal events was higher with aflibercept (three intestinal perforations) than with placebo (one intestinal fistula leading to sepsis). INTERPRETATION: This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites, but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer. VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis, and the benefit-risk balance should be thoroughly discussed for each patient. FUNDING: Sanofi Oncology.

Sequential therapy (triple drug-based induction chemotherapy followed by concurrent chemoradiotherapy) in locally advanced inoperable head and neck cancer patients - Single institute experience.

CONTEXT: India has a high incidence of head and neck squamous cell carcinoma (HNSCC) mostly presenting in advanced stage. In the majority of inoperable patients a combination of chemotherapy and radiotherapy (CRT) is considered as the treatment of choice. Adding induction chemotherapy (ICT) before CRT has shown to decrease systemic relapse. Incorporation of taxanes to the cisplatin and 5-FU-based ICT has shown increase in response rates. AIMS: To evaluate the efficacy and toxicity of triple drug-based ICT followed by CCRT in locally advanced, inoperable HNSCC in the Indian context. SETTINGS AND DESIGN: Prospective, non-controlled, observational study, a single-institute experience. MATERIALS AND METHODS: Consecutive, locally advanced inoperable HNSCC patients were put on sequential therapy consisting of docetaxel, 5-FU and cisplatin for three cycles followed by concurrent weekly cisplatin and radiotherapy for responding or stable disease patients. RESULTS: Forty-four patients were enrolled with male,female ratio of 33/44(75%) and 11/44(25%). Hypopharynx 16/44(36.36%) was the most common site followed by oral cavity 12/44(27.27%) and oropharynx 12/44(27.27%); 38/44(86.36%) patients could complete the planned treatment. Seven patients required dose reduction in ICT. As per the RECIST criteria, 16 patients had Complete Response (CR) and 15 had partial response (PR), 10 had stable disease (SD) and three had progressive disease (PD) after ICT. Thirty-eight patients received concomitant chemo radiotherapy (CCRT); 28/44 (66.63%) patients achieved CR, 10/44 (22.72 %) had PR. The main toxicity was mucositis 18/44 (40.90%) secondary to ICT. Grade III and IV hematological toxicity was seen in 16/44(36.36%), of which 6/44 (13.63%) had febrile neutropenia. CONCLUSIONS: Triple drug-based sequential therapy is tolerable in our context. In this trial from a single institute the results are very encouraging.