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Objective: The PACIFIC trial established standard therapy for patients with unresectable stage III NSCLC who did not progress after platinum-based concurrent chemoradiation therapy. However, real-world data, particularly from Latin America, remain limited. The LACOG 0120 study aimed to evaluate the efficacy and safety of consolidation therapy with durvalumab in a real-world setting in Brazil., Methods: Patients with unresectable stage III NSCLC who received chemoradiotherapy followed by durvalumab consolidation therapy through an expanded access program were evaluated. The primary objective was to assess progression-free survival (PFS). Secondary endpoints included overall survival (OS), treatment compliance, and safety, with a focus on the incidence and severity of immune-mediated adverse events (NCT04948411)., Results: Thirty-one patients from seven centers were evaluated. Median follow-up was 50.3 months (95% CI: 48.6-54.4). Median PFS was 9.9 months (95% CI: 7.3-52.4), with a 36 month-PFS of 34.5% (95% CI: 17.7-52.1). Median OS was 34.9 months (95% CI: 26.0-NR), and the 36 month-OS was 46.3% (95% CI: 25.7-64.6). Durvalumab was administered for a median of 17 cycles (10 to 24), with 45.2% of patients completing the planned therapy. The main reason for discontinuation was disease progression. Treatment-related adverse events of any grade occurred in 12 patients (38.7%), with grade 3 events reported in two (6.5%). Pneumonitis was observed in 4 patients (12.9%) - grade 3 in 1 patient., Conclusions: PFS was lower in this analysis compared to the PACIFIC trial; however, OS was similar, indicating comparable efficacy in a real-world setting among Brazilian patients with unresectable stage III NSCLC. No new safety concerns were identified.

Aims: This study evaluated the clinicopathological characteristics, treatment trends, and overall survival (OS) in male breast cancer (BC) in Sao Paulo State of Brazil., Materials and Methods: Men diagnosed with invasive breast cancer between January 2000 and June 2020 were identified from Fundação Oncocentro de Sao Paulo database encompasses data pertinent to 46 million residents of the Sao Paulo State of Brazil. Patients were described according to age, education level, clinical stage, treatment modalities, and medical practice. Categorical variables were described as percentages and frequencies. Demographic, treatment factors, and OS were associated using a Cox proportional hazard regression model while accounting for different lengths of participant follow-up. The Kaplan-Meier curves were used to display survival curves., Results: A total of 907 male BC patients were included. The age distribution at diagnosis was <51 years, 51-70 years, and >70 years in 21.5%, 51.5% and 27.0% of patients, respectively. The proportions of stages I, II, III, and IV were 19.5%, 36.6%, 31.5%, and 12.3%. For each stage I, II, III, and IV, 5- and 10-years OS were 87.9% and 77.8%, 79.9% and 58.9%, 51.6% and 24.5%, 20.0% and 5.6%, respectively. Patients who received postoperative radiotherapy experienced a significant improvement in OS (HR 0.67; 95% CI 0.53-0.84; p < 0.001). In the multivariable analysis adjusted for practice (public or private), education (low or medium/high), age, stage at diagnosis, and treatment modalities, the significant independent predictor for OS was stage at diagnosis., Conclusion: Male BC tends to be diagnosed at a more advanced stage and older age at the time of diagnosis. Age and educational level did not influence survival outcomes. Stage at diagnosis and the use of postoperative radiotherapy were factors associated with improved OS., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been recently developed and introduced into clinical practice., Methods: We retrospectively analyzed data from patients with confirmed HR+/HER2 metastatic breast cancer treated with hormonal therapy in combination with ribociclib (R), palbociclib (P), or abemaciclib (A)., Outcomes: median progression-free survival (mPFS), time to treatment discontinuation (mTTD), and objective response rate (ORR)., Results: Between January 2016 - June 2021, 142 patients were treated with an CDK4/6i (79 P, 42 R, 21 A). The median age was 59 years and 67.6% had recurrent disease. Roughly 35.2%, 36.6%, 28.2% of the patients had 1, 2 or 3+ metastatic sites, respectively, and 55.6% of the patients received CDK4/6i as a first-line treatment. The mPFS was 28m(R) vs. 14m(P) vs. 6m(A) (P = 0.002), with a higher proportion of patients receiving R in the first-line setting. However, no difference was seen when the analysis was restricted to the first-line scenario (P = 0.193). Sixty-four patients required one dose reduction, and 19 patients required two. ORR was 76.2% (R) vs 62% (P) vs 42.9% (A). More patients achieved a complete response with R and P, with no difference in the incidence of partial response and stable disease. Adverse events occurred in 94.4% of the population, with the most common grade 3-4 AE being neutropenia (59.1%)., Conclusions: Our results confirm the efficacy and tolerability of CDK4/6i in routine clinical practice. This is the first real-world data describing and comparing the efficacy and toxicity of CDK4/6i in the Brazilian population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors MMQ, RS, LJCO, and AK have no conflicts to declare. Author KPS reported consultant fees from Eurofarma and as a speaker from Novartis, AstraZeneca, Janssen, Lilly. Author MFR received honoraria from Bristol-Myers-Squibb. Author LLG reported receiving speaker bureau fees from the companies Novartis, AstraZeneca. Author RDML participates in clinical studies sponsored by the company Daiichi-Sankyo, Lilly, Roche, MSD, Bayer, GSK, Pfizer; as a speaker for AstraZeneca, Daiichi-Sankyo, Novartis, Pfizer, MSD, Lilly, Zodiac, United Medical, Grunenthal, Roche; participated in scientific events for the companies Lilly, Novartis, Roche, Fleury, Daiichi-Sankyo, Pfizer. Author MRSC reported receiving advisory board and presentations fees from Roche, AstraZeneca, Pfizer, MSD, Lilly, Gilead, BMS, Agendia, Janssen, Sanofi. Author RBS reported receiving speaker bureau fees from Agilant, AstraZeneca, Daichi-Sankyo, Eli Lilly, Pfizer, Novartis, Merck, Libbs and Roche; he has also served as a consultant/ advisor for AstraZeneca, Daichi-Sankyo, Eli Lilly, Libbs, Roche, Merck and has received support for attending medical conferences from AstraZeneca, Eli Lilly, Daichi-Sankyo, and Merck. Author MS reported consultant fees from MSD, Pfizer, AstraZeneca, Daiichi-Sankyo and Novartis. Author TSC participates in clinical studies sponsored by the company Lilly, Pfizer, Novartis, BMS; and reported receiving speaker bureau fees from AstraZeneca, Novartis, Pfizer, Novartis, Libs. Author MSM declares advisory engagements, presentations and educational expenses for Pfizer, Lilly and Novartis. DAS participates in clinical studies sponsored by the company Lilly, as a speaker at events for AstraZeneca, MSD, Novartis, Roche, Pfizer, Advisory, GSK, Roche; board advisory for Gilead. AKS participates as a sub investigator in clinical studies sponsored by the company Pfizer, Lilly, MSD, AstraZeneca, Novartis, Roche; as a speaker for Pfizer, Novartis, Lilly, AstraZeneca, Daiichi-Sankyo, MSD, Roche, Janssen, Amgen, Grunenthal., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions., Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective., Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient., Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers., Competing Interests: • Dr Oliveira has no conflicts of interest to report. • Dr Megid has no conflicts of interest to report. • Dr Mano has provided compensated consultancy services and lectures for Roche, MSD, Astra Zeneca, Novartis, Lilly-Inclone, DASA (including one for Endopredict), Fleury, Daiichi-Sankyo, Oncologia Brasil, Onconews, Instituto Oncoclínicas, and Pfizer. • Dr Magliano has no conflicts of interest to report. • Dr Sanches has provided compensated consultancy services and lectures for MSD, Astra Zeneca, Novartis, Lilly-Inclone, Daiichi-Sankyo, and Amgen. • Dr Kaliks has provided compensated consultancy services and lectures for Daiichi Sankio, Astra Zeneca, Roche, Pfizer, Fleury, BMS, and Novartis. • Dr Caleffi has provided compensated consultancy services and lectures for Novartis, Roche, Astra Zeneca, Daishii Sankyo, and Lilly. • Dr Assad has provided compensated consultancy services and lectures for Roche, MSD, Astra Zeneca, and Novartis. • Dr Correa TS has provided lectures for Libbs, Daiichi Sankio, Astra Zeneca, Pfizer, Novartis, and Lilly-Inclone. • Dr Gagliato has provided compensated consultancy services and lectures for Roche, MSD, Astra Zeneca, Novartis, Lilly, Fleury, Daiichi-Sankyo, Oncologia Brasil, Zodiac, Pfizer, Novartis, and Manual de Oncologia Clinica do Brasil. • Dr R.BS reported receiving speaker bureau fees from Agilent, AstraZeneca, Daichi-Sankyo, Eli Lilly, Pfizer, Novartis, MSD, and Roche. He has also served as a consultant/advisor for AstraZeneca, Daichi-Sankyo, Eli Lilly, Libbs, Pfizer, Roche, MSD and has received support for attending medical conferences from Astrazeneca, Roche, Eli Lilly, Daichi-Sankyo, and MSD. • Dr Testa has provided compensated consultancy services and lectures for Novartis, Roche, Pfizer, Zodiac, Lilly, MSD, Daichii-Sankyo, and AstraZeneca. She has received educational support from Pfizer, Libbs, United Medical, Lilly, Zodiac, AstraZeneca and has an institutional grant from Novartis. • Dr Bines has provided compensated consultancy services and lectures for Astra Zeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi. • Dr Daniela has provided compensated consultancy for Roche, Novartis, AstraZeneca, Lilly, GSK, Sanofi, Libbs, Eisai, Pfizer, Dr Reddy’s, United Medical, Daiichi Sankyo. She has received research funding from Amgen, Roche, GSK, L’Òreal. She has served as expert testimony for: Roche, Novartis, Pfizer, AstraZeneca, Lilly, Teva. • Dr Shimada has provided compensated consultancy for AstraZeneca, Daichii-Sankyo, Novartis, Pfizer, MSD, Lilly, Janssen, Zodiac, Grünenthal, Amgen e Roche. She has received research funding from AstraZeneca, Lilly, Novartis, Roche, MSD, Pfizer. She has received educational support from Lilly, Novartis, Roche, Fleury, Daiichi-Sankyo, Pfizer. • Dr Sahade has provided compensated consultancy services and lectures for MSD, AstraZeneca, Novartis, Daiichi-Sankyo, Oncologia Brasil and Pfizer. • Dr Argolo has provided compensated consultancy services and lectures for Novartis, Pfizer, Amgen, Roche, Libbs, AstraZeneca, Daiichi-Sankyo, Fleury and Instituto Oncoclínicas. • Dr Batista has no conflicts of interest to report. • Dr. Musse has no conflicts of interest to report. • Dr Cesca has no conflicts of interest to report. • Dr Gaudencio has no conflicts of interest to report. • Dr Araujo has no conflicts of interest to report. • Dr Moura has no conflicts of interest to report. • Dr Katz has no conflicts of interest to report., (© The Author(s), 2022.)

The survival outcomes of the FLAURA trial support osimertinib as the new standard of care for untreated patients harboring activating mutations in the epidermal growth factor receptor (EGFR). Despite the initial response, disease progression invariably occurs. Although uncommon, BRAF V600E mutation arises as a unique mechanism of resistance, and thus far, no prospective studies are available to support concurrent EGFR/BRAF blockade. We report a case of impressive radiological and ctDNA response under dabrafenib, trametinib, and osimertinib in an advanced EGFR-mutant lung adenocarcinoma patient who developed BRAF V600E as one of the acquired resistance mechanisms to second-line osimertinib. Moreover, the patient experienced remarkable clinical improvement and good tolerance to combination therapy. The present case suggests the importance of prospective studies evaluating both efficacy and safety of the combination in later line settings and points towards the potential of ctDNA to monitor resistance mechanisms and treatment benefit in clinical practice.

Objectives: to report outcomes of four cases of chemo-refractory RET-rearranged non-small cell lung carcinomas (NSCLCs) treated with alectinib in a single center., Materials and Methods: we retrospectively assessed and reported the activity and tolerability of alectinib 600 mg twice daily in advanced and chemo-refractory RET-rearranged NSCLC patients treated in a Brazilian institution. Identification of RET rearrangements was performed using the FoundationOne® next-generation sequencing (NGS) platform., Results: The four patients herein reported were white, female and non-smokers, ranging between 59-66 years of age. All patients had been previously treated with chemotherapy and were TKI naïve; three of them presented disease progression to nivolumab as well. Molecular tumor profiling showed a KIF5B-RET fusion in three patients and a CCDC6-RET in the fourth. One patient exhibited disease progression and clinical deterioration two months after treatment initiation. Disease control was documented in two patients with PFS ranging from 4 to 5 months (one partial metabolic response and one stable disease). In one of the cases, which developed oligoprogression on alectinib, radiation therapy plus post-progression alectinib were able to provide additional disease control for 9 more months. No grade 3/4 adverse events, dose reductions or discontinuation due to toxicity were documented., Conclusion: Although this is a small single center evaluation, alectinib was well tolerated and demonstrated clinical activity against advanced RET-rearranged NSCLCs, suggesting its potential role in this specific subset of malignancies. Clinical trials addressing its efficacy and the optimal dosing schedule in the present context are underway, and results are eagerly awaited., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Osteonecrosis is a multifactorial process that can affect different skeletal structures of the body. Osteonecrosis of the jaw associated with bevacizumab, steroids and bisphosphonates, alone or in combination, is a well-documented phenomenon. There are few cases of involvement of the appendicular skeleton. Magnetic resonance imaging is the most sensitive method for diagnosis. We hereby report two cases of osteonecrosis in the right tibia and in bilateral femoral heads in patients with adenocarcinoma of the lung and ovarian papillary serous carcinoma, respectively, that developed the complication after long-term bevacizumab exposure. Long-term exposure to antiangiogenic treatment may be a potential risk factor. Oncologists should be aware that osteonecrosis is a rare but real toxicity associated with bevacizumab and other antiangiogenics, which can occur in locations different from the jaw.

Histone deacetylase inhibitors (HDACi) are a relatively new class of drug that plays an important role in the epigenetic and non-epigenetic regulation in cancer, inducing death, apoptosis and cell cycle arrest in cancer cells. Although HDACi are approved only for hematologic malignancies, there are several trials in the breast cancer setting with promising results. In this review, we summarize the latest studies with HDACi in breast cancer from the emerging data in the translational research until its possible applicability in the clinical practice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation. Erlotinib was discontinued and osimertinib was initiated. Blood samples were collected at erlotinib progression and during osimertinib treatment for the detection of the activating (EGFR-exon19del) and resistance mutations (EGFR-T790M, EGFR-C797S, BRAF-V600E, METamp and ERBB2amp) in the plasma DNA using digital droplet PCR. Plasma levels of the activating EGFR-exon19del accurately paralleled the clinical and radiological progression of disease and allowed early detection of AR to osimertinib. Resistance to osimertinib coincided with the emergence of a small tumor cell subpopulation carrying the known EGFR-C797S resistance mutation and an additional subpopulation carrying amplified copies of EGFR-exon19del. Given the existence of multiple AR mechanisms, quantification of the original EGFR activation mutation, instead of the resistance mutations, can be efficiently used to monitor response to osimertinib, allowing early detection of AR. Absolute quantification of both activation and resistance mutations can provide important information on tumor clonal evolution upon progression to osimertinib. Selective amplification of the EGFR-exon19del allele may represent a novel resistance mechanism to osimertinib., (Copyright © 2017 Elsevier B.V. All rights reserved.)