Cancer Trials Ecosystem in India-Ready for Prime Time?

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials. However, there remains challenges, including a shifting regulatory environment in recent decades. With the implementation of the New Drugs and Clinical Trial Rules in 2019, India's regulatory atmosphere seems to have stabilized. In this article, we present a review of the evolving clinical trial landscape in India, highlight the current regulatory scenario, and discuss the advantages and challenges of selecting India as a potential location for conducting global oncology clinical trials.

Prevalence of EGFR Mutations in Patients With Resected Stage I-III NSCLC: Results From the EARLY-EGFR Study.

BACKGROUND: There is limited literature on the prevalence of EGFR mutations in early-stage non-small cell lung cancer (NSCLC). EARLY-EGFR (NCT04742192), a cross-sectional study, determined the prevalence of EGFR mutations in early-stage NSCLC. METHODS: This non-interventional, real-world study enrolled consecutive patients with resected stage IA-IIIB (American Joint Committee on Cancer 8th edition) NSCLC from 14 countries across Asia, Latin America, and Middle East and Africa. The primary endpoint was prevalence of EGFR mutations and secondary endpoints included prevalence of EGFR mutation subtypes and treatment patterns. RESULTS: Of 601 patients (median [range] age: 62.0 [30.0-86.0] years) enrolled, 52.7% were females and 64.2% were non-smokers. The majority had stage IA-IB NSCLC (64.1%) and adenocarcinoma histology (98.7%). Overall prevalence of EGFR mutations was 51.0%; majority reported exon-19 deletions (48.5%) followed by exon-21 L858R mutations (34.0%). Women had a higher EGFR mutation rate than men (64.0% versus 36.4%). Compared with no EGFR mutations, patients with EGFR mutations were more likely to be non-smokers (35.1% versus 60.9%) and have stage I NSCLC compared to stage II and III NSCLC (54.8% versus 47.3% and 35.6%). Systemic adjuvant therapy was planned in 33.8% patients with stage IB to IIIB disease and adjuvant chemoradiotherapy in 6.8% patients. Age ≥60 years, females, and Asians were found to have a significantly (p < 0.05) higher odds of EGFR mutations, while smoking history and stage III disease had lower odds of EGFR mutations. CONCLUSION: The EARLY-EGFR study provides an overview of EGFR mutations and subtype prevalence in patients with early-stage NSCLC. The study highlights the limited adherence to treatment guidelines suggesting an unmet need for improved adjuvant therapy.

COVID-19 and Cancer: A Comparison of the Two Important Pandemic Waves in an Indian Cancer Patients' Cohort.

Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves. This was a prospective study of all COVID-19-positive cancer patients attending our specialty out-patient department at Rajiv Gandhi Cancer Institute and Research Centre between March 2020 and November 2020 (1st wave) and April 2021 and June 2021 (second wave). All patients diagnosed to have COVID-19 by real-time polymerase chain reaction (RT-PCR) with a biopsy-proven solid organ malignancy attending the medical oncology out-patient department were included during both the waves. A total of 300 patients with proven SARS-CoV-2 infection by either RT-PCR or cartridge based nucleic acid amplification test were encountered, of which 123 were encountered during the first wave of the pandemic and 177 during the second wave. The case fatality rate of the first wave was 9.8%, with a 15-day case fatality rate of 5.6%, whereas for the second wave, it was 13% and 7.2%, respectively. Twelve patients succumbed to COVID-19 disease in the first wave and 23 succumbed in the second. There were no statistically significant correlations; however, the death in the second wave tended to occur more in younger male patients, with comorbidities and history of smoking. There was no relation with ongoing cancer-directed treatment or chemotherapy. Our study is unique in comparing characteristics of the two most important COVID-19 waves and treatment patterns in cancer patients from a single center. The second wave showed a higher CFR, hospital admission rate, and higher frequency of respiratory complications; however, there was no relation to cancer-directed therapy and COVID-19, thus reiterating the fact that cancer treatment should not be halted in the event of a COVID-19 infection.

Accuracy of endobronchial ultrasound (EBUS) in the staging of lung cancer - A comparison of staging EBUS with postoperative pathological nodal staging.

BACKGROUND: Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) has replaced mediastinoscopy as the preferred investigation for evaluating mediastinum in staging lung cancer. There is little evidence of mediastinal staging by EBUS-TBNA from India. OBJECTIVES: To study endobronchial ultrasound's diagnostic accuracy in staging lung cancer. METHODOLOGY: We retrospectively analysed patients operated on for lung cancer where EBUS was performed preoperatively for mediastinal staging. We compared the histological findings obtained from different mediastinal lymph nodes (LNs) by EBUS-TBNA with the pathology of the same LNs obtained after surgical dissection as the reference standard. RESULTS: Seventy-six patients underwent curative surgery for lung cancer. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA in predicting mediastinal metastasis were 93.9%, 40%, 99%, 80% and 94.6%, respectively. Of the 115 LNs sampled, EBUS-TBNA was false negative in six nodes, resulting in an up-staging of six patients. CONCLUSIONS: EBUS-TBNA has a high diagnostic accuracy for lung cancer staging.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor (EGFR) mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large. Additional challenges such as adequacy of tissue in case of lung core biopsies and locating suitable tumour tissues as a result of innate intratumoral heterogeneity indicate the necessity of an AI-based end-to-end pipeline capable of automatically detecting and learning more effective lung nodule features from CT images and predicting the probability of the EGFR-mutant. This will help the oncologists and patients in resource-limited settings to achieve near-optimal care and appropriate therapy. Methods: The EGFR gene sequencing and CT imaging data of 2277 patients with lung carcinoma were included from three cohorts in India and a White population cohort collected from TCIA. Another cohort LIDC-IDRI was used to train the AIPS-Nodule (AIPS-N) model for automatic detection and characterisation of lung nodules. We explored the value of combining the results of the AIPS-N with the clinical factors in the AIPS-Mutation (AIPS-M) model for predicting EGFR genotype, and it was evaluated by area under the curve (AUC). Findings: AIPS-N achieved an average AP50 of 70.19% in detecting the location of nodules within the lung region of interest during validation and predicted the score of five lung nodule properties. The AIPS-M machine learning (ML) and deep learning (DL) models achieved AUCs ranging from 0.587 to 0.910. Interpretation: The AIPS suggests that CT imaging combined with a fully automated lung-nodule analysis AI system can predict EGFR genotype and identify patients with an EGFR mutation in a cost-effective and non-invasive manner. Funding: This work was supported by a grant provided by Conquer Cancer Foundation of ASCO [2021IIG-5555960128] and Pfizer Products India Pvt. Ltd.

Comparison of RECIST and iRECIST criteria in patients with advanced lung cancer treated with nivolumab.

Background: Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents. Purpose: To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns. Material and Methods: Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test. Results: Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant. Conclusion: Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India.

BACKGROUND: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). MATERIALS AND METHODS: This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. RESULTS: Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n â€‹= â€‹6951; 30.1%) followed by Klebsiella pneumoniae (n â€‹= â€‹5801; 25.1%) and Pseudomonas aeroginosa (n â€‹= â€‹3041; 13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. CONCLUSION: This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.

Primary pulmonary NUT midline carcinoma: An elusive and a rare diagnostic entity.

Nuclear protein in testis (NUT) midline carcinoma is a poorly differentiated tumor, is more common in midline anatomic sites, and involves young adults and children mainly. Primary pulmonary NUT midline carcinoma (NMC) is a rare and poorly defined entity in the prevailing literature. Being a highly aggressive and fatal neoplasm, it gets incumbent for the oncologists and the pathologists to be aware of this entity as it holds distinct management protocol and prognosis. Currently, BET inhibitors (BETi) and histone deactylase inhibitors have shown promising results as targeted therapies in clinical trials in head and neck NMC. We present a case report of NMC of primary pulmonary location in a young male with widespread bony metastasis.

Differential clinicopathological features, treatments and outcomes in patients with Exon 19 deletion and Exon 21 L858R EGFR mutation-positive adenocarcinoma non-small-cell lung cancer.

The most common oncogenic driver in non-small-cell lung cancer (NSCLC) is the epidermal growth factor receptor (EGFR) gene mutations that occur more frequently among Asians (30%-50%) as opposed to Caucasians (10%-15%). Lung cancer is one of the most prevalent cancers in India, with a reported adenocarcinoma positivity ranging between 26.1% and 86.9% in NSCLC patients. The prevalence of EGFR mutations in adenocarcinoma patients (36.9%) in India is higher than that of Caucasian patients and lower than that of East Asian patients. The exon 19 deletion (Ex19del) is more common than exon 21 L858R mutations in Indian patients with NSCLC. Studies have shown that the clinical behaviour of patients with advanced NSCLC differs between EGFR Ex19del and exon 21 L858R mutation status. In this study, we investigated the differences in clinicopathological features and survival outcomes after first line and second-line treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs) in NSCLC patients with Ex19del and exon 21 L858R EGFR mutation status. This study also focuses on the role and potential benefits of dacomitinib, a second-generation irreversible EGFR TKI, in patients with Ex19del and exon 21 L858R EGFR mutation-positive advanced NSCLC in Indian settings.

Clinical management of stage III non-small cell lung cancer in India: An expert consensus statement.

Non-small cell lung cancer (NSCLC) is considered the most common type of lung cancer (>80% of all lung cancers); patients are often diagnosed at advanced stages of the disease. The management of NSCLC is considered challenging owing to variations in size, an extension of the tumors, involvement patterns, and classification. Although adequate literature and guidelines are available on the management of NSCLC in several countries, an Indian perspective on stage III NSCLC management is lacking. We used the modified Delphi approach to form consensus statements. A thorough literature search was done. The authors then convened and deliberated over published literature, available guidelines, and clinical judgment. Recommendation statements were formed for different clinical scenarios. These statements were sent as a form of survey to other oncologists, and their responses were recorded and mentioned. Evidence-based statements were formed for diagnosing and managing stage III NSCLC. These recommendation statements cover various aspects-surgical, radiation, and medical treatment in various clinical scenarios including adjuvant, neoadjuvant, and consolidation therapies.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non-Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis.

PURPOSE: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. MATERIALS AND METHODS: Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. RESULTS: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. CONCLUSION: Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort.

OBJECTIVE: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). METHODS: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. RESULTS: The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. CONCLUSION: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. ADVANCES IN KNOWLEDGE: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.

Expert Consensus Recommendations on Biomarker Testing in Metastatic and Nonmetastatic NSCLC in Asia.

INTRODUCTION: Most published guidelines for genomic biomarker testing in NSCLC reflect the disease epidemiology and treatments readily available in Europe and North America. Nevertheless, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the EGFR occur at a higher prevalence in Asia than in other world regions. Although medical associations such as the International Association for the Study of Lung Cancer, European Society for Medical Oncology, and American Society of Clinical Oncology have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia. METHODS: This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts for clinicians working in Asia to improve patient care. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1, and others are discussed. RESULTS: These recommendations are divided into nonmetastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma. Owing to the higher prevalence of EGFR mutations in Asia, the experts emphasized the need for EGFR testing to include not just common mutations (exon 19 deletions and L858R substitutions) but also other uncommon EGFR mutations. In addition to the assessment of biomarkers in the tumor tissue, the role of assessing tumor biomarkers by liquid biopsy is discussed. CONCLUSION: This consensus provides practical recommendations for biomarker testing in nonmetastatic and metastatic Asian NSCLC patients.

KRAS mutated Non-Small Lung Carcinoma: A Real World Context from the Indian subcontinent.

BACKGROUND: KRAS, although a common variant of occurrence (~20% of non-small-cell lung carcinoma [NSCLC]) has been untargetable, owing to the molecular structure which inherently prevents drug binding. KRAS mutations in NSCLC are associated with distinct clinical profiles including smokers and mucinous histology. KRAS G12C mutations account for ~40% KRAS altered NSCLC, but NSCLC being a geographically diverse disease, the features may be distinct in this part of the world. This is a single-center experience of KRAS-mutated NSCLC including clinical, imaging, pathologic features, and treatment patterns and outcomes. METHODS: This is a single-center retrospective study of KRAS-mutated NSCLC. The clinicopathological features and outcomes were retrieved and collated from the medical record archives of the hospital. RESULTS: Fifty (30.6%) patients with advanced-stage NSCLC with alterations in the KRAS gene were enrolled in the 163 patients who were tested for KRAS alterations. The median age was 61 years. Molecular detection revealed three main types of KRAS mutations viz-a-vis: G12C in 17 (34%), G12V in 9 (18%), and G12D in 6 (12%) patients. Comparing G12C versus the non-G12C mutated cases, co-mutations were common in the non-G12C subgroup (p < 0.05). Among the 36, who were treated at our center, all received chemotherapy as the first line with a median progression-free survival (PFS)of 5.4 months. The PFS of G12C was higher than the non-G12C subgroup (6.4 vs 3.8 months). CONCLUSION: This is the largest single-center experience from the Indian subcontinent for KRAS-mutated NSCLC with distinct clinical features. It highlights the unmet need for G12C inhibitors in our country, where prevalence is equivalent to the West.

A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib.

ABSTRACT: In-frame fusions in NTRK genes, with intact kinase domain, have been reported to occur at higher frequencies in rare tumors like infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinoma, whereas they occur at very low frequencies in common malignancies like NSCLC and colon cancers (0.1%-1%). Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene. More than 50 fusion partners have been described, and only in-frame fusions result in constitutive ligand-independent kinase activity leading to oncogenesis. The commonly reported NTRK fusions in the lung include SQSTM1-NTRK1, ETV6-NTRK3, and SQSTM1-NTRK3. Detection of these rests on the use of conventional modalities like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however, accurate characterization requires direct sequencing methods. We report an interesting case of an NTRK fusion-positive NSCLC, exhibiting good response to entrectinib.

Analysis of Clinical Outcomes of Patients with Soft Tissue Sarcoma.

The aim of this study was to evaluate the outcome of patients with soft tissue sarcoma of the extremity and abdominal wall. This is the retrospective analysis of patients from a prospectively maintained data base from a single institute. We identified 79 patients with intermediate- to high-grade soft tissue sarcomas who were treated at our institute between Jan 2015 and July 2018. Low-grade tumors were excluded. There were 60 males and 19 females with a mean age of 44.6 years. Of the 79 sarcomas, 50 were in the lower limb and 24 in the upper limb and 5 were in abdominal wall. The commonest subtypes were undifferentiated pleomorphic sarcoma (n = 21) and synovial sarcoma (n = 19). Only 9 patients had metastatic disease at presentation. All 79 patients underwent surgical resection with an intent to achieve clear margins. Amputation was done in 19 patients while wide excision of the tumor was done in 60 patients. Adjuvant radiotherapy was given in 49 patients while adjuvant chemotherapy was given in 35 patients. At last follow-up (73 patients), 48 patients are alive without disease, 9 are alive with disease, 12 patients had died of disease, and 4 patients died due to other causes. Overall survival (OS) for 3 year is 77.6%, and estimated mean survival is 55.05 months. Relapse-free surviva (RFS)l at 3 year is 74.3%, and estimated mean RFS is 51.78. The only independent factor that affected the OS was the dimension of primary tumor (p = 0.02). For disease-free survival, the independent factors that affected outcome were stage at presentation (p = 0.04) and dimension of the tumor (p = 0.04). Short-term results shown by this study shows good outcome in patient with intermediate- to high-grade sarcomas when multidisciplinary approach is utilized for the management. Patients who had metastatic disease at presentation did worse than patients who did not.

Ramucirumab in Indian Patients with Advanced Gastric Cancer-Does Borderline Performance Status and Heavy Burden of Disease in Real World Practice Impact Clinical Benefit?

Vikas OstwalBackground Ramucirumab is considered a standard of care as second-line therapy (CT2) in advanced gastric cancers (AGCs). The aim of this study was to assess practice patterns and outcomes with ramucirumab among Indian patients with AGCs. Materials and Methods A computerized clinical data entry form was formulated by the coordinating center's (Tata Memorial Hospital) medical oncologists and disseminated through personal contacts at academic conferences as well as via email for anonymized patient data entry. The data was analyzed for clinical characteristics, response rates, and survival outcomes. Results A total of 26 physicians contributed data, resulting in 55 patients receiving ramucirumab and being available for analysis. Median age was 53 years (range: 26-78), 69.1% of patients had greater than two sites of disease, and baseline Eastern Cooperative Oncology Group's performance score (ECOG PS) ≥ 2 was seen in 61.8% of patients. Ramucirumab was used as monotherapy in 10.9% of patients, while the remaining 89.1% received ramucirumab combined with chemotherapy. Median event-free survival (EFS) and median overall survival (OS) with ramucirumab were3.53 months (95% CI: 2.5-4.57) and 5.7 months (95% CI: 2.39-9.0), respectively. Common class specific grade adverse events seen with ramucirumab included gastrointestinal (GI) hemorrhage (9.1% - all grades) and uncontrolled hypertension (Grade 3/4 - 3.6%). Conclusions Ramucirumab appears to have similar efficacy in Indian AGC patients when compared with real-world data from other countries in terms of median EFS, but OS appears inferior due to more patients having borderline ECOG PS and high metastatic disease burden. GI hemorrhages appear more common than published data, although not unequivocally related to ramucirumab.

Analysis of Spatial Heterogeneity of Responses in Metastatic Sites in Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher's exact test was used to compare categorical variables, and a Kruskal-Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue.

Immunotherapy in advanced non-small-cell lung cancer (NSCLC) after progression on chemotherapy: real-world results from a prospective institutional cohort.

Objective: To analyze the outcomes of patients receiving immunotherapy (IO) with advanced non-driver mutated non-small-cell lung cancer (NSCLC) after progression on systemic treatment. Methods: The overall survival (OS), progression-free survival (PFS) and best response to IO of 64 patients who met our inclusion criteria were analyzed. Results: Median follow-up, OS and PFS were 35.9, 7.1 and 3.2 months, respectively. On uni- and multi-variable analysis, better ECOG PS and fewer extra-thoracic metastases were associated with prolonged OS and PFS. Response to IO was associated with prolonged OS, while thoracic radiotherapy and isolated CNS involvement were associated with prolonged PFS. ECOG PS, thoracic radiotherapy and PDL1 status significantly influenced the likelihood of response to IO. Overall, 30% patients experienced any grade toxicity. Conclusion: Our results are concordant with reported trial outcomes and support the application of IO in Indian patients.

Several clinical trials have demonstrated favorable results with immunotherapy in patients with lung cancer who do not have a mutation in their tumors. However, clinical trials are often designed to provide the best chance for a trial drug/intervention to demonstrate effectiveness. Therefore, they usually include relatively healthier patients compared to what clinicians see in their practice. To demonstrate the efficacy of a drug outside a clinical trial, a real-world analysis is performed, which is reported in this article. We analyzed lung cancer patients treated with immunotherapy at our institution and found comparable efficacy to reported clinical trials. This was important because the trials did not include any patients from our country. We also found that patients with fewer sites of involvement outside the lung and those who received radiotherapy to the lung (either during or before receiving immunotherapy) survived longer without disease progression.