Eribulin mesylate in Indian patients: A single center experience.

BACKGROUND: Eribulin mesylate is the latest addition in the armamentarium of management of metastatic breast cancer (MBC) with a unique mechanism of action. Although the multicentric EMBRACE trial suggests significant overall survival benefit from this novel drug, its effectiveness in Indian population is yet to be evaluated. MATERIALS AND METHODS: Presented here is a single center experience of eight patients who were administered eribulin for MBC. Patients had received a median of 3 prior chemotherapies before eribulin administration. The median dose of eribulin therapy was 5 cycles (range: 2–6 cycles). RESULTS: The objective response rate was 75% (CR in one and PR in five out of eight patients). Response was seen across all subtypes of patients. Eribulin was well tolerated. No serious adverse events were reported. CONCLUSION: Eribulin conferred good response rates with satisfactory tolerability profile in Indian patients. Its use in earlier lines and in combination with other drugs may achieve deeper and longer responses.

Genomic profiling in a homogeneous molecular subtype of non‑small cell lung cancer: An effort to explore new drug targets.

BACKGROUND: Patients’ who are positive for kinase domain activating mutations in epidermal growth factor receptor (EGFR) gene, constitute 30–40% of non‑small cell lung cancer (NSCLC), and are suitable candidates for Tyrosine Kinase Inhibitor based targeted/personalized therapy. In EGFR non‑mutated subset, 8–10% that show molecular abnormalities such as EML4‑ALK, ROS1‑ALK, KIP4‑ALK, may also derive the benefit of targeted therapy. However, 40% of NSCLC belong to a grey zone of tumours that are negative for the clinically approved biomarkers for personalized therapy. This pilot study aims to identify and classify molecular subtypes of this group to address the un‑met need for new drug targets in this category. Here we screened for known/novel oncogenic driver mutations using a 46 gene Ampliseq Panel V1.0 that includes Ser/Thr/ Tyr kinases, transcription factors and tumor suppressors. METHODS: NSCLC with tumor burden of at least 40% on histopathology were screened for 29 somatic mutations in the EGFR kinase domain by real‑time polymerase chain reaction methods. 20 cases which were EGFR non‑mutated for TK domain mutations were included in this study. DNA Quality was verified from each of the 20 cases by fluorimeter, pooled and subjected to targeted re‑sequencing in the Ion Torrent platform. Torrent Suite software was used for next generation sequencing raw data processing and variant calling. RESULTS: The clinical relevance and pathological role of all the mutations/variants that include SNPs and Indels was assessed using polyphen‑2/SIFT/PROVEAN/mutation assessor structure function prediction programs. There were 10 pathogenic mutations in six different oncogenes for which annotation was available in the COSMIC database; C420R mutation in PIK3CA, Q472H mutation in vascular endothelial growth factor receptor 2 (VEGFR2) (KDR), C630W and C634R in RET, K367M mutation in fibroblast growth factor receptor 2 (FGFR2), G12C in KRAS and 4 pathogenic mutations in TP53 in the DNA binding domain (E285K, R213L, R175H, V173G). CONCLUSION: Results suggest, a potential role for PIK3CA, VEGFR2, RET and FGFR2 as therapeutic targets in EGFR non‑mutated NSCLC that requires further clinical validation.

Prevalence of KRAS mutations in metastatic colorectal cancer: A retrospective observational study from India.

BACKGROUND: One of the genetic alterations implicated in tumor progression in colorectal cancers (CRCs) are abnormalities in Kristen Rat Sarcoma (KRAS) gene. Evaluation of KRAS mutation status is an important prognostic factor and has predictive value in deciding first line therapy based on monoclonal antibodies such as Cetuximab and Panitumumab in metastatic CRCs. MATERIALS AND METHODS: In this retrospective study, we analyzed 7 different somatic mutations in Exon 2 of KRAS gene in 299 unselected incidental CRC patients who visited the hospital for clinical management during the period 2009–2013. Most of the tumors were primarily originating from colon and rectum; nevertheless, there were a few from rectosigmoid, sigmoid, ceacum and anal canal in the study group. Genomic DNA extracted from paraffin embedded tumor tissues was screened for 7 point mutations located in Codons 12 and 13 of KRAS gene, using Scorpions amplified refractory mutation system real time polymerase chain reaction technology. Statistical analysis was performed to assess bivariate relationship between different variables that includes: mutation status, mutation type, tumor location, tumor morphology, age and sex. RESULTS: Prevalence of mutation in Codons 12 and 13 was 42.8% in the study group. Well‑differentiated tumors had significantly more mutation positivity than moderately and poorly differentiated tumors (P = 0.001). 92% of the mutations were from Codon 12 and 8% in Codon 13. Glycine to Arginine was relatively more common in rectosigmoid followed by ceacum, while Glycine to Alanine mutation was relatively more prevalent in sigmoid, followed by rectum and rectosigmoid. CONCLUSION: The results suggest a prevalence of KRAS mutation at 42.8% in Indian population indicating that this testing is very crucial for targeted therapy management in metastatic CRC in India. Further analysis on mutation status of other homologues such as NRAS and downstream partner, v‑raf murine sarcoma viral oncogene homolog B1, would add value to understanding the role of anti‑epidermal growth factor receptor therapy in CRC management.

Epidermal growth factor receptor mutation in non-small-cell lung carcinomas: A retrospective analysis of 1036 lung cancer specimens from a network of tertiary cancer care centers in India.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation plays a vital role in the prognosis of patients with lung cancer. However, there is a dearth of studies on EGFR mutation in Indian population. In this retrospective study conducted at a network of tertiary cancer care centers across India, we evaluated the proportion of EGFR mutation in patients with non‑small‑cell lung carcinomas (NSCLC). MATERIALS AND METHODS: A total of 1036 cases of non‑small lung cancer were assessed for EGFR mutation status using Scorpion amplified refractory mutation system real time polymerase chain reaction method from fine needle aspiration cytology core biopsy, pleural fluid and cell blocks. For a few cases, macro dissection of tumor from H and E slides was also performed for EGFR analysis. EGFR Status was assessed for the most commonly known driver mutations in Exons 18, 19, 20 and 21, which contributes to a total of 29 somatic mutations including the resistance mutation T790M. RESULTS: Around 39% of the cohort was female and 61% were male. Mutation was positive in 40.3% and negative (wild type) in 59.7%. There was 1.8% mutation in exon 18, 24.6% in exon 19, 1.6% in exon 20 and 12.8% in exon 21. 38.2% had a mutation in a single site and 1.1% had a mutation in two sites. Overall mutation was significant in females (50.5% vs. 33.9%) compared with males (c2 = 28.3, P < 0.001). Mutation was significant in exon 21 (16.8% vs. 10.3%, c2 = 9.44, P = 0.002) and exon 19 (30.7% vs. 20.7%, c2 = 13.2, P < 0.001) in females compared with males. CONCLUSION: EGFR is expressed differentially/ mutated in patients with NSCLC. Further studies to unravel the predictors for acquired genetic alterations of EGFR are needed.

Hepatoblastoma: Experience from a single center.

Background: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. Aims: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. Settings and Design: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. Materials and Methods: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. Results: There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. Conclusions: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.