Adjuvant platinum versus capecitabine for residual, invasive, triple-negative breast cancer: Patient-reported outcomes in ECOG-ACRIN EA1131.

BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.

Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131.

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.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

Posterior reversible encephalopathy syndrome in a postpartum woman with acute lymphoblastic leukaemia after intrathecal methotrexate.

Posterior reversible encephalopathy syndrome (PRES) is the most common neurological complication occurring in children undergoing induction chemotherapy for acute lymphoblastic leukaemia (ALL) but is increasingly recognised to occur in adults as well. Here, we report a woman who presented with B-cell ALL (B-ALL) at the time of delivery and developed PRES 1 day after receiving intrathecal (IT) methotrexate (MTX) that rapidly resolved. She subsequently received IT MTX without recurrence of neurological symptoms. This case represents the first case of PRES in a postpartum B-ALL patient receiving IT MTX, demonstrates that re-treatment with MTX in this case could be done safely and highlights the risk of PRES in adults treated for B-ALL.

Left Ventricular Ejection Fraction Screening and Clinical Decision-making in Metastatic HER2-positive Breast Cancer.

BACKGROUND: Antibodies against human epidermal growth factor receptor 2 (HER2) affect metastatic breast cancer cells and cardiac myocytes. Guidelines recommend evaluation of cardiac ejection fraction (EF) every 3 months despite little supporting evidence for this need. We assessed the impact of EF screening on clinical practice. PATIENTS AND METHODS: We carried out retrospective analysis of patients with HER2-positive metastatic breast cancer receiving HER2-directed therapy to assess the impact of aggressive cardiac screening on management decisions. RESULTS: Data for 128 patients were analyzed. The median number of EF screenings in the first year of therapy was 3 (range=1-8). A total of 29 patients had an asymptomatic decrease in EF. These patients had more EF screenings, more exposure to anthracyclines or left-sided radiation, were more likely to receive a cardiology consult and have an angiotensin converting enzyme inhibitor added to their therapy. Ninety patients underwent aggressive screening; this was not associated with cessation of HER2 therapy (p=0.92). CONCLUSION: Routine EF screening did not have an impact on decisions regarding HER2 therapy in patients with metastatic breast cancer. Given the known benefit of HER2 treatment, reducing the frequency of cardiac screening may be reasonable.

Differences in Physicians' Verbal and Nonverbal Communication With Black and White Patients at the End of Life.

CONTEXT: Black patients are more likely than white patients to die in the intensive care unit with life-sustaining treatments. Differences in patient- and/or surrogate-provider communication may contribute to this phenomenon. OBJECTIVES: To test whether hospital-based physicians use different verbal and/or nonverbal communication with black and white simulated patients and their surrogates. METHODS: We conducted a randomized factorial trial of the relationship between patient race and physician communication using high-fidelity simulation. Using a combination of probabilistic and convenience sampling, we recruited 33 hospital-based physicians in western Pennsylvania who completed two encounters with prognostically similar, critically and terminally ill black and white elders with identical treatment preferences. We then conducted detailed content analysis of audio and video recordings of the encounters, coding verbal emotion-handling and shared decision-making behaviors, and nonverbal behaviors (time interacting with the patient and/or surrogate, with open vs. closed posture, and touching the patient and physical proximity). We used a paired t-test to compare each subjects' summed verbal and nonverbal communication scores with the black patient compared to the white patient. RESULTS: Subject physicians' verbal communication scores did not differ by patient race (black vs. white: 8.4 vs. 8.4, P-value = 0.958). However, their nonverbal communication scores were significantly lower with the black patient than with the white patient (black vs. white: 2.7 vs. 2.9, P-value 0.014). CONCLUSION: In this small regional sample, hospital-based physicians have similar verbal communication behaviors when discussing end-of-life care for otherwise similar black and white patients but exhibit significantly fewer positive, rapport-building nonverbal cues with black patients.

The Language of End-of-Life Decision Making: A Simulation Study.

BACKGROUND: Framing is known to influence decision making. OBJECTIVE: The study objective was to describe language used by physicians when discussing treatment options with a critically and terminally ill elder. METHODS: High-fidelity simulation was used, involving an elder with end-stage cancer and life-threatening hypoxia, followed by a debriefing interview. Subjects were hospitalist, emergency medicine, and critical care physicians from three academic medical centers. Measures were observation of encounters in real time followed by content analysis of simulation and debriefing interview transcripts. During the simulation we identified the first mention ("broaching") of principal treatment options--intubation and mechanical ventilation (life-sustaining treatment [LST]) and palliation in anticipation of death (palliation)--and used constant comparative methods to identify language used. We identified physician opinions about the use of LST in this clinical context during the debriefing interviews, and compared language used with opinions. RESULTS: Among 114 physician subjects, 106 discussed LST, 86 discussed palliation, and 84 discussed both. We identified five frames: will (decided), must (necessary), should (convention), could (option), and ask (elicitation of preferences). Physicians broached LST differently than palliation (p<0.01), most commonly framing LST as necessary (53%), while framing palliation as optional (49%). Among physicians who framed LST as imperative (will or must), 16 (30%) felt intubation would be inappropriate in this clinical situation. CONCLUSIONS: In this high-fidelity simulation experiment involving a critically and terminally ill elder, the majority of physicians framed the available options in ways implying LST was the expected or preferred choice. Framing of treatment options could influence ultimate treatment decisions.