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.

Effect of a Structured Teaching Module Including Intensive Prophylactic Measures on Reducing the Incidence of Capecitabine-Induced Hand-Foot Syndrome: Results of a Prospective Randomized Phase III Study.

LESSONS LEARNED: A structured teaching module including intensive prophylactic measures to alleviate hand-foot syndrome (HFS) during capecitabine therapy is feasible but ineffective at protecting patients from HFS. Pharmacologic therapeutic interventions should be investigated for the management of this complication. BACKGROUND: Capecitabine-induced hand-foot syndrome (HFS) has a detrimental effect on quality of life. The effect of a structured teaching module including intensive prophylactic measures was evaluated. METHODS: This non-crossover phase III double-blinded clinical trial randomized patients in a 1:1 ratio to either a control group or to a group administered a structured teaching model including intensive prophylactic measures on HFS administered by a trained oncology nurse at regular intervals (case) versus standard information on HFS care administered by treating clinician (control). The primary endpoint was comparison of fraction of patients in both arms developing at least grade 2 HFS. RESULTS: Between June 15, 2016, and April 4, 2018, 280 patients (140 to case and 140 to control) were enrolled. The median number of capecitabine chemotherapy cycles was eight; 269 patients (96%) were evaluable for HFS, of whom 89 patients (33.08%) developed at least grade 2 HFS (grade 2 HFS, 73 patients [26.1%]; grade 3 HFS, 16 patients (5.7%}). There was no difference in at least grade 2 HFS between evaluable case and control arms of the study (control group, 45/135 [33.3%]; case, 44/134 [32.8%]; p = .93). CONCLUSION: The use of a structured teaching module including intensive prophylactic measures was feasible, but this did not reduce the incidence and severity of capecitabine-induced HFS.

Clinical practice and outcomes in advanced gastrointestinal stromal tumor: Experience from an Indian tertiary care center.

BACKGROUND: Management of advanced Gastrointestinal stromal tumors (GIST) has been revolutionized with the use of Imatinib guided by mutation analysis. Data from India remains scarce. MATERIALS AND METHODS: Patients with metastatic GIST who were treated at Department of Gastro-intestinal & Hepaticopancreaticobiliary Oncology Unit at Tata Memorial Hospital, Mumbai between December, 2004 and December 2015 were included in the analysis. Clinical and radiological data was retrieved from stored medical records and charts. RESULTS: A total of 83 patients with metastatic GIST were available for analysis. Median age was 54 years with a 3:1 male predominance. Stomach was the most common site of primary with liver being the most common site of metastasis. c-Kit mutation analysis results were available for 44 patients with exon 11 mutant being the most common mutation. With a median follow up of 33 months, the 10 years estimated progression free and overall survival (OS) was 18% and 51% respectively. Overall response rate to first line imatinib was 37.6% and estimated 3 years OS to first line therapy was significantly better for Exon 11 mutated patients (p=0.016). 34 patients received second line therapy in the form of either sunitinib, pazopanib or increased dose imatinib with a clinical benefit rate of 73.5%. C-Kit mutated patients had a better median OS compared to non mutated patients. CONCLUSIONS: GIST diagnosed and treated in the Indian subcontinent appears to show improved outcomes. The importance of c-Kit mutation analysis in determining the prognosis and outcomes of patients with advanced GIST is emphasized.

Treatment of advanced Gall bladder cancer in the real world-can continuation chemotherapy improve outcomes?

BACKGROUND: Gemcitabine-Platinum doublet chemotherapy is the standard of care in patients with locally advanced inoperable and metastatic (LA/M) Gall bladder cancers (GBC). METHODS: Consecutive patients with LA/M GBC treated with Gemcitabine-Cisplatin (GC) or Gemcitabine-Oxaliplatin (GO) as first line palliative chemotherapy from January 2013 to June 2015 were retrospectively analysed. Patients who were able to continue chemotherapy beyond 6-8 cycles were separately compared to those who were potential candidates for this approach, but chose not to continue chemotherapy. RESULTS: A total of 396 patients received first line palliative chemotherapy during the period of analysis, 276 patients (69.6%) were unable to complete 6-8 cycles of chemotherapy, while 120 patients (30.4%) were potential candidates for continuing chemotherapy. Seventy patients (n=120; 58.3%) received a median of 4 cycles of continuation chemotherapy. Median overall survival (OS) for the entire cohort was 7.65 months [95% confidence interval (CI), -7.14 to 8.16], while median event free survival (EFS) was 4.53 months (95% CI, -4.23 to 4.83). Patients receiving continuation chemotherapy had a statistically improved median OS compared to all other patient cohorts, 14.88 months (95% CI, -12.48 to 17.27; P=0.005 on multivariate analysis). Burden/number of sites of metastases, receiving of continuation chemotherapy, fit and able to receive second line chemotherapy (CT2) were identified on multivariate analysis as prognostic factors for OS. CONCLUSIONS: OS in our study appeared lower than published literature, but a group of patients were identified whose survival could be prolonged by continuing chemotherapy. Easily available factors can predict prognosis of GBC undergoing first line palliative chemotherapy.

Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis.

BACKGROUND: Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). METHODS: The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. RESULTS: A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. CONCLUSION: Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO.

Metastatic anorectal melanomas - An exploratory retrospective analysis on the benefits of systemic therapy versus best supportive care in a resource-limited setting from India.

AIM: Data regarding the optimal management of metastatic anorectal melanoma (mARM) is scarce. The primary aim was to evaluate the potential benefits of systemic therapy in mARM. MATERIALS AND METHODS: This is a retrospective analysis of all mARM who presented between July 2013 and June 2015 at the Department of GI Medical Oncology, Tata Memorial Hospital. RESULTS: Of a total of 37 patients, twelve patients were planned for best supportive care (BSC) only while the remaining 25 patients received systemic therapy. The median overall survival (OS) for the whole cohort was 27 weeks. The OS was significantly better in patients who received first-line therapy as compared to those who were offered BSC (median OS: 14 vs. 33 weeks; P = 0.04). Patients with PS of 1 did significantly better than PS of 2 more (OS 70 vs. 17 weeks; P = 0.015). CONCLUSION: mARM should be offered chemotherapy, especially in good performance patients. Paclitaxel/Platinum or Capecitabine/Temozolomide regimens can be considered as the preferred regime in the resource-limited setting where immunotherapy may not be a feasible option.