PURPOSE Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine. PATIENTS AND METHODS Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine. RESULTS Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum. CONCLUSION Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.

Background The hypomethylating agents (HA), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the activity of these agents in a real world setting is not well studied. Methods We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002–2011 treated with HAs either as 1st line (n=34), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charlson Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results Frontline response rate (CR+CRi) was 26.5%, median overall survival (OS) was 3.4 (95% CI 1.3–7.4) months, with 18% alive at one year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6% versus 26.5%, p=0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 (CI 4.8–10.3) months. In the consolidation cohort OS was 13.8 (CI 8.0 – 21.6) months with one patient in remission more than 30 months from diagnosis. Conclusion These data suggest prior cytotoxic therapy decrease marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over one year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.

Introduction Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. Methods We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002–2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. Results In this series, 144 patients were ≥60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, p<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non diabetic patients, p =0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6–15.2) times. Discussion Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), in patients with locally advanced rectal cancer, occurs in 15-27% of patients. Because blood cell counts and albumin are a direct indicator of the host environment, a response to nCRT might be predicted by these markers. This study was carried out to determine whether the neutrophil to albumin ratio (NAR) was predictive of pCR in veteran patients. Ninety-eight patients with rectal cancer who underwent standard nCRT, followed by TME were analyzed. Pre-nCRT and post-nCRT hematologic data were collected. Univariate and multivariate analyses were carried out. Kaplan-Meier curves were constructed with our primary endpoint of pCR. Male patients (99%), age 62.4±9.1 years, BMI=27.4±5.9 kg/m, rectal cancer distance from anal verge=7.1±4.5 cm (SD), interval between nCRT and TME=8 weeks, 55% patients=low anterior resection, 95% received 5-fluorouracil, and all patients received radiation, with 15% achieving a pCR. Univariate analysis showed that pre-nCRT carcinoembryonic antigen (15.8±45.1 vs. 3.5±5.3 ng/dl; P=0.002) and the pre-nCRT NAR (16.4±4.8 vs. 14.2±1.6; P=0.002) were associated with pCR. On multivariate analysis, pre-nCRT carcinoembryonic antigen (odds ratio=0.41, 95% confidence interval 0.22-0.77) and pre-nCRT NAR (odds ratio=0.76, 95% confidence interval 0.60-0.97) remained independent predictors of pCR. Overall survival between nonresponders and pCR patients at 1, 5, and 10 years was 96, 62, and 44% versus 93, 85, and 61%, P=0.13, and disease-free survival was 95, 60, and 47% versus 93, 85, and 61%, P=0.17; respectively. Our study shows that the pre-nCRT NAR is an independent predictor of pCR. These findings should be applied to other cohorts to determine its validity and reliability for use as a potential predictor of pCR.