Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSE: Comprehensive genomic profiling (CGP) assay is increasingly used in low-middle-income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays. METHODS: This was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. RESULTS: During 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%). CONCLUSION: We observed that in a low-middle-income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.

Comparison of the Efficacy, Safety, Pharmacokinetic and Immunogenicity of UJVIRA (ZRC-3256, Trastuzumab Emtansine) With the Kadcyla (Trastuzumab Emtansine) in the Treatment of HER2-Positive Metastatic Breast Cancer: A Randomized, Open-Label, Multicenter Study in India.

BACKGROUND: UJVIRA is the first DCGI approved biosimilar of trastuzumab emtansine (Kadcyla) which may offer an alternative cost-effective treatment option for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients in India. This article summarizes the available clinical evidence supporting the biosimilarity of UJVIRA and Kadcyla with respect to efficacy, pharmacokinetic, safety, and immunogenicity. MATERIALS AND METHODS: A phase 3, randomized, open-label, active-controlled study was conducted at 31 sites across India. A total of 168 patients were enrolled and randomized to receive either UJVIRA or Kadcyla. Of which, only first 50 patients were included in pharmacokinetic assessment. UJVIRA or Kadcyla were administered at a dose of 3.6 mg/kg by intravenous infusion every 3 weeks (21 days) for 8 cycles or until disease progression or unmanageable toxicity, whichever was earlier. The study assessed efficacy (ORR), safety, pharmacokinetics, and immunogenicity. RESULTS: The ORR at the end of Week 24 was 37.76% in the UJVIRA and 33.33% in the Kadcyla group. The risk difference was 4.42% [-12.01, 20.85]. It met noninferiority margin of -15%. The pharmacokinetic parameters were comparable between groups. No antidrug antibody was detected in any of the treatment groups. The overall safety profile in terms of TEAEs and laboratory abnormalities was also comparable between the treatment groups. CONCLUSION: Results demonstrated biosimilarity between UJVIRA and Kadcyla in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Therefore, UJVIRA could prove to be a cost-effective treatment alternative for HER2-positive metastatic breast cancer patients in India.

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.

Can multiparametric MRI and FDG-PET predict outcome in diffuse brainstem glioma? A report from a prospective phase-II study.

PURPOSE: To study the impact of multiparametric MRI and (18)F-FDG-PET on the outcome of children with diffuse intrinsic pontine gliomas (DIPG). MATERIALS AND METHODS: Imaging data from a phase-II prospective therapeutic study in children with newly diagnosed DIPG were considered for evaluation. They included baseline MRI with contrast enhancement before treatment. Functional imaging included MR spectroscopy, MR perfusion and FDG-PET studies. All patients (n = 20) had baseline MRI and 11 patients had FDG-PET. Response was assessed by MRI and PET 4 weeks after therapy. Baseline imaging findings were correlated with survival. Presence or absence of adverse parameters on MRI (heterogeneous contrast enhancement, hyperperfusion or increased choline:NAA ratio) was used to develop a cumulative radiological prognostic index (RPI). Sensitivity and specificity of each imaging modality in tumour grading was estimated. RESULTS: The cumulative RPI was able to classify the patients into different grades and was predictive of overall survival (p = 0.02). MR perfusion also predicted survival (p = 0.039). Sensitivity and specificity of MRI and FDG-PET to detect low-grade gliomas were low to moderate (33-66%), but moderate to high in detecting high-grade gliomas (50-100%). Baseline FDG uptake on PET scan did not correlate with survival (p = 0.7). CONCLUSIONS: Cumulative RPI was able to classify tumours into different grades and predicted clinical outcome. At baseline, MR hyperperfusion indicated a shorter survival for DIPG patients. Sensitivity and specificity of imaging modalities to detect low-grade gliomas were poor.

NEO adjuvant chemotherapy in breast cancer: What have we learned so far?

Neoadjuvant chemotherapy (NACT) in breast cancer has undergone continuous evolution over the last few decades to establish its role in the combined modality management of these tumors. The process of evolution is still far from over. Many questions are still lurking in the minds of oncologists treating breast cancer. This review analyzes the evidence from metaanlyses, major multiinstitutional prospective trials, retrospective institutional series and systematic reviews in breast cancer to determine the current standards and controversies in NACT. The most effective drugs, their advantages, issues and controversies in delivery as well as the criteria for response are reviewed. A summary of evidence-based consensus is presented and unresolved aspects are discussed.

Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma.

PURPOSE: To present outcome data in a prospective study of radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in children with diffuse intrinsic pontine gliomas (DIPGs). METHODS AND MATERIALS: Pediatric patients with newly diagnosed DIPGs were prospectively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m(2), Days 1-42). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m(2), Days 1-5) was given every 28 days to a maximum of 12 cycles. Response was evaluated clinically and radiologically with magnetic resonance imaging and positron emission tomography scans. RESULTS: Between March 2005 and November 2006, 20 children (mean age, 8.3 years) were accrued. Eighteen patients have died from disease progression, one patient is alive with progressive disease, and one patient is alive with stable disease. Median overall survival and progression-free survival were 9.15 months and 6.9 months, respectively. Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients, leucopenia in 2, and vomiting in 7. Transient Grade II skin toxicity developed in the irradiated fields in 18 patients. During the adjuvant TMZ phase, Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient. Patients with magnetic resonance imaging diagnosis of a high-grade tumor had worse survival than those with a low-grade tumor (p = 0.001). Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not (p = 0.048). CONCLUSIONS: TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone. Further clinical trials should explore novel treatment modalities.