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18th February 2022
Adjuvant pembrolizumab added to chemotherapy post surgery significantly improves event-free survival compared to chemotherapy alone. This was the conclusion of a study by researchers from the Centre of Experimental Cancer Medicine, Barts Cancer Institute, London, UK.
Triple negative breast cancer constitutes 10-15% of female breast cancers and is a more aggressive cancer with more frequent recurrence and worse survival compared with the non-triple negative form. Clinical trial data has revealed improved disease-free survival with postoperative chemotherapy in patients with either triple-negative or HER2-positive breast cancer who had residual disease after neoadjuvant chemotherapy. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would increase the proportion of patients with early triple-negative breast cancer who had a pathological complete response after surgery was unclear until publication in 2020, of the KEYNOTE-522 trial. The trial concluded that the percentage of patients with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy.
For the present study, the authors have reported on an updated analysis of the KEYNOTE-522 trial and in particular, event-free survival as well as additional efficacy and updated safety information. Participants were adults with confirmed triple negative breast cancer or those with newly diagnosed and previously untreated non-metastatic disease with primary tumour and regional lymph node involvement. During the adjuvant phase, patients with previously untreated stage II or III triple negative breast cancer, were randomised 2:1 to receive either pembrolizumab (the pembrolizumab–chemotherapy group) or placebo (the placebo–chemotherapy group), administered once every 3 weeks. After surgery, patients received either pembrolizumab or placebo and chemotherapy every 3 weeks for up to nine cycles. The primary endpoint was pathological complete response and event-free survival.
Adjuvant Pembrolizumab and event-free survival
A total of 1174 patients were randomly assigned to either arm and during follow-up, 123 (15.7%) patients assigned to the pembrolizumab arm had an event or died compared to 93 (23.8%) in the placebo-chemotherapy arm.
The estimated event-free survival after 36 months was 84.5% in the adjuvant pembrolizumab group and 76.8% in the placebo arm, giving a hazard ratio, HR, for an event or death = 0.63, 95% CI 0.48 – 0.82, p < 0.001.
Data on overall survival were described as immature at the time of the analysis and the estimated overall survival at 36 months was 89.7% in the adjuvant pembrolizumab group and 86.9% in the placebo-chemotherapy group. With respect to safety, the authors reported that the reported adverse events were consistent with the established safety profile of both pembrolizumab and chemotherapy.
The authors concluded that among those with early triple negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy and then followed by adjuvant pembrolizumab after surgery, was associated with a significantly longer event-free survival than neoadjuvant chemotherapy alone.
Schmid P et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer N Engl J Med 2022
16th December 2021
Ethic and socioeconomic disparities in survival outcomes have been highlighted in an analysis of newly diagnosed children and young adults with acute lymphoblastic leukaemia (ALL). This was the main finding from a study by researchers from Institute for Health Policy, Evaluation and Management, University of Toronto, Canada, presented at ASH 2021.
Health disparities are major issue for racial, ethnic, and socioeconomically disadvantaged groups and although outcomes in childhood ALL have steadily improved, disparities based on ethnicity and socioeconomic (SES) factors appear to persist.
For the present study, the Canadian team sought to identify the presence of any persistent inequities by race/ethnicity and SES in childhood ALL in the largest cohort ever assembled for this purpose. They identified a cohort of newly-diagnosed patients with ALL, ranging in age from 0 to 40 years enrolled in trials between 2004-2019. Race/ethnicity was categorised as non-Hispanic white vs. Hispanic vs. non-Hispanic Black vs. non-Hispanic Asian vs. Non-Hispanic other.
SES was proxied by insurance status: United States (US) Medicaid (public health insurance for low-income individuals) vs. US other (predominantly private insurance) vs. non-US patients (mainly jurisdictions with universal health insurance). Event-free and overall survival (EFS, OS) were compared across race/ethnicity and SES. The relative contribution of disease prognosticators (age, sex, white blood cell count, lineage, central nervous system status, cytogenetics, end Induction minimal residual disease) were examined with Cox proportional hazard multivariable models of different combinations of the three constructs of interest (race/ethnicity, SES, disease prognosticators) and examining hazard ratio (HR) attenuation between models.
The study cohort included 24,979 children, adolescents, and young adults with ALL. A total of 13,872 (65.6%) of the whole cohort were Non-Hispanic White patients, followed by 4354 (20.6%) Hispanic patients and 1517 (7.2%) non-Hispanic Black patients. Those insured with US Medicaid were 6944 (27.8%).
The 5-year EFS was 87.4% among non-Hispanic White patients vs. 82.8% among Hispanic patients (hazard ratio, HR = 1.37, 95% CI 1.26 – 1.49; p<0.0001] and 81.9% among non-Hispanic Black patients. The outcomes for non-Hispanic Asian patients were similar to those of non-Hispanic White patients.
US patients on Medicaid had inferior 5-year EFS as compared to other US patients (83.2% vs. 86.3%, HR = 1.21, 95% CI 1.12 – 1.30, p<0.0001) while non-US patients had the best outcomes, with a 5-year EFS of 89%.
There was substantial imbalance in traditional disease prognosticators (e.g. T-cell lineage) across both race/ethnicity and SES, and of race/ethnicity by SES. For example, T-lineage ALL accounted for 17.6%, 9.4%, and 6.6% of Non-Hispanic Black, Non-Hispanic White, and Hispanic patients respectively (p<0.0001).
Multivariable analysis showed how EFS among Hispanic patients was substantially attenuated by the addition of disease prognosticators and the hazard ratio reduced from HR 1.37 to 1.17 and was further (but not fully) attenuated by the subsequent addition of SES (HR 1.11).
In contrast, the increased risk among non-Hispanic Black children was minimally attenuated by both the addition of disease prognosticators and subsequent addition of SES (HR reduction of 1.45 to 1.38 to 1.32). Similarly, while the superior EFS of non-US insured patients was substantially attenuated by the addition of race/ethnicity and disease prognosticators (HR 0.79 to 0.94), increased risk among US Medicaid patients was minimally attenuated by the addition of race/ethnicity or disease prognosticators (HR 1.21 to 1.16).
OS disparities followed similar patterns but were consistently worse than in EFS, particularly among patients grouped as non-Hispanic other.
The authors concluded that there were substantial disparities in survival outcomes by race/ethnicity and SES and that these disparities varied between specific disadvantaged groups., adding that future studies are required to identify specific drivers of survival disparities that may be mitigated by targeted interventions.
Gupta S et al. Racial, Ethnic, and Socioeconomic Factors Result in Disparities in Outcome Among Children with Acute Lymphoblastic Leukemia Not Fully Attenuated By Disease Prognosticators: A Children’s Oncology Group (COG) Study. ASH Conference 2021