Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Achieving complete metabolic response in stage IV lung adenocarcinoma with chemotherapy, nivolumab, ipilimumab, and salvage SBRT: A case report.

Oncogene-negative, PDL1-negative metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges due to its complexity and resistance to conventional therapies. The case report presented addresses a 55-year-old male patient with oncogene-negative, PDL1-negative stage IV lung adenocarcinoma, showcasing an exceptional complete metabolic response to a multimodality treatment combining double immune checkpoint inhibition (ICI) and chemotherapy, followed by salvage stereotactic body radiotherapy (SBRT). The patient underwent a treatment regimen incorporating two cycles of carboplatin, pemetrexed, nivolumab, and ipilimumab followed by nivolumab, and ipilimumab maintenance. After a partial response, SBRT was applied to persistent lesions, achieving a complete metabolic response. This case highlights the potential of combining dual ICI with chemotherapy and SBRT in treating oncogene-negative, PDL1-negative NSCLC underscoring the importance of multimodality treatment strategies.

Clinicopathological and Genomic Identification of Breast Cancers with No Impact on Mortality.

BACKGROUND: Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. PATIENTS AND METHODS: To identify them, a retrospective observational study was carried out selecting patients without any palpable tumor and without axillary involvement, and a genomic analysis was performed with PAM50. RESULTS: The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumors and in 9 (9.47%) luminal B tumors smaller than 1 cm, and in HER2 and basal type tumors, there were no metastatic events (20-year DMFI of 1.00). CONCLUSION: Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumor size less than 1 cm. Therefore, de-escalation of treatment should be considered.

Correlation between breast cancer subtypes determined by immunohistochemistry and n-COUNTER PAM50 assay: a real-world study.

PURPOSE: Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments. Several surrogate classifications have been proposed for distinguishing between the luminal A and B subtypes. This study determines the accuracy of local immunohistochemistry (IHC) techniques for classifying HR-positive/HER2-negative (HR+/HER2-) tumors according to intrinsic subtypes using the nCOUNTER PAM50 assay as reference and the HR status definition according the ASCO/CAP recommendations. METHODS: Molecular subtypes resulting from nCOUNTER PAM50 performed in our laboratory between 2014 and 2020 were correlated with three different proxy surrogates proposed in the literature based on ER, PR, HER2, and Ki67 expression with different cut-off values. Concordance was measured using the level of agreement and kappa statistics. RESULTS: From 1049 samples with the nCOUNTER test, 679 and 350 were luminal A and B subtypes, respectively. Only a poor-to-fair correlation was observed between the three proxy surrogates and real genomic subtypes as determined by nCOUNTER PAM50. Moreover, 5-11% and 18-36% of the nCOUNTER PAM50 luminal B and A tumors were classified as luminal A and B, respectively, by these surrogates. CONCLUSION: The concordance between luminal subtypes determined by three different IHC-based classifiers and the nCOUNTER PAM50 assay was suboptimal. Thus, a significant proportion of luminal A and B tumors as determined by the surrogate classifiers could be undertreated or over-treated.

Características clínico-patológicas y supervivencia de pacientes con cáncer de mama de riesgo muy bajo / Clinicopathological characteristics and survival results of patients with ultralow risk breast cancer

Antecedentes y objetivo: La universalización del cribado mamográfico ha incrementado el diagnóstico de cánceres de mama con pronóstico excelente. La ausencia de tumor palpable les confiere un riesgo muy bajo de mortalidad por cáncer de mama. El objetivo del estudio fue identificar subgrupos con muy buena evolución a largo plazo.Pacientes y métodosIdentificamos pacientes con muy buena evolución mediante estudio descriptivo, observacional y retrospectivo. Los criterios de riesgo muy bajo fueron la procedencia del cribado mamográfico, sin tumor palpable, el fenotipo tumoral y la afectación ganglionar.ResultadosDe 746 pacientes con carcinoma de mama, con ganglios negativos, entre 2001 y 2015, 110 (14,75%) procedían del cribado con tumores no palpables. Ochenta y ocho (80%) eran hormonosensibles, 10 (9,10%) triples negativos y 11 (10%) HER2. La mediana de seguimiento fue 10 años (3,5-17). Solo tres pacientes desarrollaron metástasis, no hubo recidivas loco-regionales, siete presentaron segundos tumores primarios y hubo cuatro muertes, dos por cáncer de mama y dos por otras causas. El intervalo libre de metástasis a distancia (ILMD) fue 95,60% (intervalo de confianza (IC) 95% 90,70-100,50); 96,30% (IC 95% 91,21-99,39) en 88 tumores hormonosensibles, 100% en 34 hormonosensibles de grado histológico 1 (aproximación a luminales A) y 94,40% (IC 95% 86,76-102,04) en 54 de grado 2-3 (luminales B). En los triples negativos y HER2 fue 100%. En tumores menores y mayores de 1 cm fue 100% y 95,50% (IC 95% 89, 42-101,58).ConclusionesLas pacientes con tumores no palpables, detectados en el cribado mamográfico tienen un riesgo de recurrencia muy bajo. La buena evolución en los subgrupos luminal A, triple negativo, HER2 y menores de 1 cm puede explicar la eficacia del tratamiento, pero también los hace candidatos a desescalar su tratamiento. (AU)

Background and objective: To identify subgroups with good progress over an extended period, we used diagnostic screening, tumour palpability, tumour phenotype, and node involvement.Patients and methodsWe identified patients with good progress by means of a descriptive, observational and retrospective study.ResultsOf 746 patients diagnosed with node-negative breast cancer between 2001 and 2015: 110 (14.75%) had non-palpable screening-diagnosed tumours; 88 (80%) were endocrine-sensitive, 10 (9.10%) were triple-negative and 11 (10%) were HER2. Only 3 patients developed metastases, and there were 4 deaths: 2 from breast cancer and 2 from other causes. The distant recurrence-free interval (DRFI) was 95.60%: 100% in 34 endocrine-sensitive histological grade 1 (equivalent to luminal A) tumours, and 94.40% (95% CI 86.76–102.04) in 54 grade 2–3 (luminal B) tumours. In triple-negative and HER2 cases, it was 100%. In tumours <1 cm it was 100%, and >1 cm it was 95.50% (95% CI 79.42–100.98).ConclusionsPatients with non-palpable tumours detected by mammogram screening have ultralow risk. The good progress in the luminal A, triple-negative, HER2, and less than 1 cm subgroups may explain the efficacy of the treatment but it also makes them candidates to de-escalation of their treatment. (AU)

Clinicopathological characteristics and survival results of patients with ultralow risk breast cancer. / Características clínico-patológicas y supervivencia de pacientes con cáncer de mama de riesgo muy bajo.

BACKGROUND AND OBJECTIVE: To identify subgroups with good progress over an extended period, we used diagnostic screening, tumour palpability, tumour phenotype, and node involvement. PATIENTS AND METHODS: We identified patients with good progress by means of a descriptive, observational and retrospective study. RESULTS: Of 746 patients diagnosed with node-negative breast cancer between 2001 and 2015: 110 (14.75%) had non-palpable screening-diagnosed tumours; 88 (80%) were endocrine-sensitive, 10 (9.10%) were triple-negative and 11 (10%) were HER2. Only 3 patients developed metastases, and there were 4 deaths: 2 from breast cancer and 2 from other causes. The distant recurrence-free interval (DRFI) was 95.60%: 100% in 34 endocrine-sensitive histological grade 1 (equivalent to luminal A) tumours, and 94.40% (95% CI 86.76-102.04) in 54 grade 2-3 (luminal B) tumours. In triple-negative and HER2 cases, it was 100%. In tumours <1 cm it was 100%, and >1 cm it was 95.50% (95% CI 79.42-100.98). CONCLUSIONS: Patients with non-palpable tumours detected by mammogram screening have ultralow risk. The good progress in the luminal A, triple-negative, HER2, and less than 1 cm subgroups may explain the efficacy of the treatment but it also makes them candidates to de-escalation of their treatment.

Experiences with Prescribing Large Quantities of Systemic Anticancer Therapy Near Death.

Background: The most important decision after diagnosing terminal cancer is whether to provide active therapy or withhold treatment. Objective: To analyze the aggressiveness of care by evaluating systemic anticancer therapy (SACT) given near to death, describing this care and identifying factors that determine its use. Design: This involves retrospective observational cohorts study. Setting/Subjects: This involves patients with metastatic tumors who died at a University Hospital in Spain between 2015 and 2016. Measurements: Data obtained from prescribing oncologists and patients' clinical records, type of cancer, and information on treatment. The dependent variable used was the interval between the date of the last dose and date of death. Results: Ninety-four (32.60%) of 288 patients received SACT in the last month of life. This cohort had a higher frequency of lung cancer (OR: 1.58; CI 95%: 1.14-2.18), received more care from oncologist 2 (OR: 1.50; CI 95%: 1.08-2.08), had fewer last-line treatment cycles (OR: 1.28; CI 95%: 1.13-1.45), a lower subjective response (OR: 3.13; CI 95%: 1.34-7.29), less clinical benefit (OR: 2.38; CI 95%: 1.04-5.55), more visits to the Emergency Department (OR: 1.59; CI 95%: 1.06-2.38), and less care from the Palliative Care Unit (OR: 4.55; CI 95%: 2.69-7.70). In multivariate analysis, the predictors of having received SACT close to death remained: receiving fewer cycles of treatment (OR: 1.28; CI 95%: 1.12-1.47) and less palliative care (OR: 4.54; CI 95%: 2.56-7.69). Conclusions: A third of cancer patients received SACT in the last month of life with less efficacy and poorer quality of care than patients not receiving it.

Evaluación del riesgo clínico, no genómico y resultados de supervivencia en el carcinoma de mama hormonosensible, HER-2 negativo, con ganglios negativos / Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, lymph node negative breast cancer

Antecedentes y objetivos: En el cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, la presencia de un riesgo genómico bajo permite tratar solo con hormonoterapia adyuvante, obteniendo unas excelentes tasas de supervivencia. La justificación de este estudio es demostrar que también se obtienen unas excelentes tasas de supervivencia tratando solo con hormonoterapia adyuvante mediante la evaluación del riesgo clínico. Pacientes y métodos: Estudio descriptivo, observacional y retrospectivo entre 2006 y 2016 de la cohorte de cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, tamaño del tumor mayor de 1cm o entre 0,6 y 1cm con características desfavorables. Revisión retrospectiva de los registros de salud. Datos de mortalidad del Registro Nacional de Defunciones. Resultados: Un total de 203 pacientes fueron evaluables para la supervivencia. Ciento veintitrés (60,50%) fueron tratadas solo con hormonoterapia adyuvante, 77 (37,90%) con quimioterapia-hormonoterapia, una (0.50%) solo con quimioterapia y 2 (1%) no recibieron ningún tratamiento. La tasa de supervivencia global a los 5 años fue del 97% (intervalo de confianza [IC] del 95% 94-100). La tasa de intervalo libre de metástasis a distancia fue del 94% (IC 95% 90-98). En el subgrupo de pacientes tratadas solo con hormonoterapia la tasa de supervivencia global y del intervalo libre de metástasis a distancia a los 5 años fue del 98% (IC 95% 95-100) y 97% (IC 95% 93-100), respectivamente. Conclusiones: Las pacientes con cáncer de mama hormonosensible, HER-2-negativo, con ganglios negativos, tratadas solo con hormonoterapia según su riesgo clínico, obtienen resultados de supervivencia similares a los descritos cuando son tratadas solo con hormonoterapia según su riesgo genómico

Background and objectives: In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. Patients and methods: A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. Results: A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Conclusions: Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk

Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, lymph node negative breast cancer. / Evaluación del riesgo clínico, no genómico y resultados de supervivencia en el carcinoma de mama hormonosensible, HER-2 negativo, con ganglios negativos.

BACKGROUND AND OBJECTIVES: In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. PATIENTS AND METHODS: A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. RESULTS: A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. CONCLUSIONS: Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk.