Rajani Priya Yedla

PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). RESULTS Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC. CONCLUSION Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among the women. Most commonly used chemotherapy regimen is Doxorubicin and Cyclophosphamide (AC) which carries significant risk of febrile neutropenia. The aim of the study is to identify the incidence of febrile neutropenia and its effects on the delivery of chemotherapy in patients receiving following AC chemoregimen without primary prophylaxis. MATERIALS AND METHODS: We retrospectively analyzed the case records of the localized breast cancer patients who were treated with AC chemoregimen without primary prophylaxis for febrile neutropenia. RESULTS: = 0.001) no significant association was found with age, co-morbidities, menopausal status, body surface area and stage of the cancer. There were no treatment delays or dose reductions because of febrile neutropenia. CONCLUSION: The incidence of FN with AC chemotherapy in breast cancer patients is relatively less in the present study. Routine primary prophylaxis is not recommended as this chemotherapy falls in to low risk category for FN but can be considered for patients with ECOG PS > 1. If the diagnosis of febrile neutropenia and institution of appropriate measures are prompt, FN did not affect the delivery of chemotherapy and thus compromise survival.

Introduction Acute promyelocytic leukemia (APL) has transformed from a highly fatal disease to a highly curable one. Induction deaths continue to represent one of the major impediments in modern therapy of APL. Sepsis, hemorrhage, and differentiation syndrome are the major complications during induction therapy in APL. The present study reports the incidence and prognostic factors of major complications during induction chemotherapy in patients with newly diagnosed APL. Materials and Methods The present study was a single institutional, observational, retrospective study. All cases of APL diagnosed by morphology and confirmed by RT PCR (PML RARα) were included in this study. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25. Results A total of 73 patients were analyzed. The median age at presentation was 30 years (range, 3–60 years) with a female to male ratio of 1.02:1. The most common symptom at presentation was fever (80%), followed by fatigue (56%) and gum bleeding (37%). The majority of the patients at presentation were high risk (42.4%), followed by intermediate risk (38.4%) and low risk (19.2%). Fifty-seven (78%) patients achieved complete hematological remission and 16 (22%) succumbed during induction chemotherapy. Infection was the most common cause of induction death (50%), followed by hemorrhage (37.5%) and differentiation syndrome (12.5%). On univariate analysis of prognostic factors, bcr3 variant, grade 3/4 bleeding during induction, and low levels of albumin at presentation were significant for induction mortality (p = 0.034, 0.041, and 0.008 respectively). On multivariate analysis, only serum albumin < 3.5 g/dL was an independent predictor for induction mortality (p = 0.043). Conclusion The majority of patients were high risk at presentation. Sepsis was the most common complication during induction and also the leading cause of induction death. Identifying induction complications at the earliest and providing aggressive supportive measures can further improve outcomes in APL.

Abstract Background: Acute promyelocytic leukemia (APL) accounts for approximately 10% of acute myeloid leukemia(AML) cases in adults. With the advent of targeted therapy like all- trans retinoic acid (ATRA) and arsenic trioxide, survival rates have improved leading to cure in majority of patients. The present study was designed to analyze the outcomes in newly diagnosed APL. Aims and objectives: The primary objective of this study was to analyze overall survival and relapse rate in APL. Secondary objective was to study the parameters impacting outcomes in APL. Materials and methods: All newly diagnosed patients with APL between January 2005 and December 2017 were retrospectively analyzed. Diagnosis of APL was confirmed by demonstration of PML-RARA translocation by polymerase chain reaction or fluorescence in situ hydridization. Risk stratification was done using Sanz risk. Event free survival was defined as the time from diagnosis till relapse, death or lost to follow up. Overall survival was defined as time from diagnosis till death or lost to follow up. Statistical analysis was done using SPSS software, v.25. Overall survival curves were plotted using the Kaplan-Meier method. INCLUSION CRITERIA: All cases of APL diagnosed by morphology and confirmed by RT PCR (PML RARα) were included in this study. EXCLUSION CRITERIA: Age ≤ 18yrs Death within 72 hours of admission / not taken treatment Prior chemotherapy or radiotherapy for the treatment of malignancy. Results: Data of 1396 AML patients between 2005 and 2017 was collected, of which 190(13.6%) patients had APL. Of 190 patients, 111 patients who met inclusion and exclusion criteria were analyzed. The median age at presentation was 33 years (range,19-60). The male female ratio was 1.01:1. The median duration of symptoms at presentation was 15 days (range, 3-180). According to Sanz risk grouping, high, intermediate and low risk were seen in 48 (43.1%), 46 (42.4%), 17(14.5%) patients respectively. The baseline characteristics are tabulated in Table 1. Of 111 patients, 96 (86.5%) patients received induction chemotherapy with ATRA and daunorubicin and 15(13.5%) patients received ATRA and arsenic trioxide. Induction mortality was 23(20.7%). Eighty-eight (79%) patients survived induction chemotherapy, of which 87(98.8%) were in complete molecular remission (CMR) at the end of consolidation. At a median follow up of 30 months, the event free survival rate, overall survival rate and relapse rate were 72%, 74.7% and 9% respectively. The overall survival rate in low-intermediate and high-risk groups were 84.1% and 62.5% respectively. Of eight patients who relapsed, five patients received second line chemotherapy and attained second CMR (100%). On univariate analysis, the strongest predictors for OS were high risk and bcr3 variant(p=0.007, p=<0.001 respectively). On multivariate analysis, only high risk was significant for overall survival (p=0.02). Conclusion: Majority of APL patients were high risk at presentation. High risk and bcr3 variant had significant impact on survival outcome in APL. As relapse rates were low and second CMR can be achieved with salvage chemotherapy in majority of patients, improving induction outcomes will further improve survivals in APL. Disclosures No relevant conflicts of interest to declare.