Abemaciclib plus non-steroidal aromatase inhibitor or fulvestrant in women with HR+/HER2- advanced breast cancer: Final results of the randomized phase III MONARCH plus trial.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02763566).

The usefulness of CanAssist Breast over Ki67 in breast cancer recurrence risk assessment.

BACKGROUND: Assessment of Ki67 by immunohistochemistry (IHC) has limited utility in clinical practice owing to analytical validity issues. According to International Ki67 Working Group (IKWG) guidelines, treatment should be guided by a prognostic test in patients expressing intermediate Ki67 range, >5%-<30%. The objective of the study is to compare the prognostic performance of CanAssist Breast (CAB) with that of Ki67 across various Ki67 prognostic groups. METHODS: The cohort had 1701 patients. Various risk groups were compared for the distant relapse-free interval (DRFi) derived from Kaplan-Meier survival analysis. As per IKWG, patients are categorized into three risk groups: low-risk (<5%), intermediate risk (>5%-<30%), and high-risk (>30%). CAB generates two risk groups, low and high risk based on a predefined cutoff. RESULTS: In the total cohort, 76% of the patients were low risk (LR) by CAB as against 46% by Ki67 with a similar DRFi of 94%. In the node-negative sub-cohort, 87% were LR by CAB with a DRFi of 97% against 49% by Ki67 with a DRFi of 96%. In subgroups of patients with T1 or N1 or G2 tumors, Ki67-based risk stratification was not significant while it was significant by CAB. In the intermediate Ki67 (>5%-<30%) category up to 89% (N0 sub-cohort) were LR by CAB and the percentage of LR patients was 25% (p < 0.0001) higher compared to NPI or mAOL. In the low Ki67 (≤5%) group, up to 19% were segregated as high-risk by CAB with 86% DRFi suggesting the requirement of chemotherapy in these low Ki67 patients. CONCLUSION: CAB provided superior prognostic information in various Ki67 subgroups, especially in the intermediate Ki67 group.

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India.

CONTEXT: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. SETTINGS AND DESIGN: Retrospective analysis. MATERIALS AND METHODS: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. RESULTS: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3-4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. STATISTICAL ANALYSIS USED: SPSS software version 20. CONCLUSION: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted.

Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study.

BACKGROUND: GP2013 is a rituximab biosimilar developed to stringent development guidelines, including non-clinical and preclinical investigations and clinical trials in rheumatoid arthritis and follicular lymphoma. We aimed to compare the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of GP2013 plus cyclophosphamide, vincristine, and prednisone (GP2013-CVP) with rituximab-CVP (R-CVP) in patients with follicular lymphoma. METHODS: In this phase 3, multinational, double-blind, randomised, controlled trial, adults (aged 18 years or older) with previously untreated, advanced stage (Ann Arbor stage III or IV) follicular lymphoma of WHO histological grades 1, 2, or 3a were randomly assigned (1:1) using interactive response technology to eight cycles of GP2013-CVP or R-CVP (combination phase), followed by monotherapy maintenance in responders for a 2-year period. Randomisation was stratified by Follicular Lymphoma International Prognostic Index risk group and geographic region. The primary endpoint was comparability in overall response, with equivalence concluded if the entire 95% CI was within a margin of -12% to 12%. The primary endpoint was analysed using the per-protocol set, which included all patients who received at least one (partial or complete) dose of investigational treatment and who did not have any major protocol deviations. The trial is registered with ClinicalTrials.gov, number NCT01419665, and is ongoing. FINDINGS: Between Dec 1, 2011, and Jan 15, 2015, 858 patients were screened for eligibility. 314 patients were randomly assigned to GP2013, of whom 312 were given GP2013, and 315 were assigned to reference rituximab. Median follow-up was 11·6 months (IQR 5·8-18·2) for the primary analysis. The primary endpoint, equivalence of overall response, was met (271 [87%] of 311 patients with GP2013 and 274 [88%] of 313 patients with reference rituximab achieved an overall response; difference -0·40% [95% CI -5·94 to 5·14]). Occurrence of adverse events and serious adverse events was similar between the treatment groups (289 [93%] of 312 patients in the GP2013-CVP group had an adverse event and 71 [23%] of 312 patients had a serious adverse event; 288 [91%] of 315 patients in the R-CVP group had an adverse event and 63 [20%] had a serious adverse event). The most common adverse event was neutropenia (80 [26%] of 312 patients in the GP2013-CVP group and 93 [30%] of 315 patients in the R-CVP group in the combination phase and 23 [10%] of 231 patients in the GP2013-CVP group and 13 [6%] of 231 patients in the R-CVP group in the maintenance phase). The most common grade 3 or 4 adverse event during the combination and maintenance phase was neutropenia (55 [18%] of 312 patients in the GP2013-CVP group and 65 [21%] of 315 patients in the R-CVP group in the combination phase and 17 [7%] of 231 patients in the GP2013-CVP group and nine [4%] of 231 patients in the R-CVP group in the maintenance phase). The occurrence of anti-drug antibodies was similar in the treatment groups (five [2%] of 268 patients in the GP2013-CVP; three [1%] in the R-CVP group). INTERPRETATION: Our results show that GP2013 represents a viable rituximab biosimilar candidate for patients with previously untreated advanced follicular lymphoma. The introduction of biosimilars provides additional therapeutic options with potential to increase access to effective and life-saving biological therapies such as rituximab. FUNDING: Hexal.

Can the Use of Bone Marrow Parameters Improve the Efficacy of Risk Prediction Scores in Chronic Myeloid Leukemia in Imatinib Era?

INTRODUCTION: Many attempts have been made to develop risk prediction scores for chronic myeloid leukemia in chronic phase (CML-CP) to identify the subgroup with a poorer response to therapy to enable early intensification of treatment. Because the bone marrow (BM) provides a more sensitive reflection of the disease process, we hypothesized that using BM parameters in the Sokal and European Treatment and Outcome Study (EUTOS) risk scores could improve their efficacy in an imatinib-treated population. MATERIALS AND METHODS: We analyzed cases of CML-CP for their response and survival outcomes with imatinib using risk groupings determined by the Sokal and EUTOS scores using peripheral blood (PB) or BM parameters (Sokal-PB, Sokal-BM, EUTOS-PB, and EUTOS-BM). RESULTS: A total of 371 cases were analyzed. The concordance for risk groups was greater for the EUTOS scores (81.9%) than for the Sokal scores (68.1%) using PB versus BM parameters. For all 4 risk scores, the predictive efficacy was statistically significant. EUTOS-PB and EUTOS-BM could better prognosticate for progression-free survival (PFS) and overall survival (OS) between the low- and high-risk groups (P < .0001). However, with the Sokal risk score, the use of BM parameters improved the prognostic capacity for PFS between the low- and intermediate-risk groups, with a statistically significant difference (P = .025), but not for OS (P = .88). CONCLUSION: The use of BM parameters, a simple method that is feasible in routine clinical practice could improve the prognostic efficacy of the Sokal score for PFS but not for OS in low- and intermediate-risk groups. Further research to improve the sensitivity of risk scores for CML-CP prognosis and attempts at risk-directed therapy is warranted.

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy.

CONTEXT: Carcinoma cervix is a leading cause of cancer in Indian females where 15%-60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. SETTINGS AND DESIGN: The study design was a retrospective analysis. MATERIALS AND METHODS: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). RESULTS: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. STATISTICAL ANALYSIS USED: It was carried out by SPSS software version 20. CONCLUSION: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research.

Predictive and Prognostic Implications of Variant Philadelphia Translocations in CML: Experience From a Tertiary Oncology Center in Southern India.

INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results. MATERIALS AND METHODS: We retrospectively analyzed our data from January 2002 to December 2014. Patients with vPh in chronic phase of CML (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival and their data were compared with data of patients with classical Ph translocation (cPh). RESULTS: Of 615 patients diagnosed with CML-CP, 72 patients (11.7%) showed vPh. Most common chromosomes involved in these translocations were 14 (13.9%), 11 (12.5%), 19 (9.7%), and 7 (8.3%). Rates of complete hematological response, complete cytogenetic response, and major molecular response were not statistically different between the groups. At 5 years, event-free survival, failure-free survival, progression-free survival, and overall survival were 60% versus 67.9%, 62.7% versus 69.7%, 84.7% versus 92.1%, and 87.5% versus 92.4%, respectively, in vPh and cPh. The differences in survival were statistically not significant. CONCLUSION: To our knowledge, this is the largest series of variant translocations in CML-CP, pertaining to the Indian population. Our data suggest that the presence of vPh in CML has no significant effect in predicting response to imatinib as well as in prognosticating survival.

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era-experience from a tertiary oncology centre in Southern India.

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.