Purpose Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response. Anastrozole was continued until surgery, which occurred 3-5 weeks post palbociclib exposure. Later patients received additional 10-12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression and mutation profiles. The primary endpoint was Complete Cell Cycle Arrest (CCCA: central Ki67<2.7%). Results Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs C1D1 26%, p<0.001). Palbociclib enhanced cell cycle control over anastrozole monotherapy regardless of luminal subtype (A vs B) and PIK3CA status with activity observed across a broad range of clinicopathological and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with non-luminal subtypes and persistent E2F-target gene expression. Conclusions Palbociclib is an active anti-proliferative agent for early-stage breast cancer resistant to anastrozole, however, prolonged administration may be necessary to maintain its effect.

PURPOSEEvidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts.PATIENTS AND METHODSPatients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression.RESULTSForty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B).CONCLUSIONNeratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.

There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.

IMPORTANCE Most patients with advanced-stage cancer develop impairment and pain-driven functional losses that jeopardize their independence. OBJECTIVE To determine whether collaborative telerehabilitation and pharmacological pain management improve function, lessen pain, and reduce requirements for inpatient care. DESIGN, SETTING, AND PATIENTS The Collaborative Care to Preserve Performance in Cancer (COPE) study was a 3-arm randomized clinical trial conducted at 3 academic medical centers within 1 health care system. Patient recruitment began in March 2013 and follow-up concluded in October 2016. Participants (N = 516) were low-level community or household ambulators with stage IIIC or IV solid or hematologic cancer. INTERVENTIONS Participants were randomly assigned to the (1) control arm, (2) telerehabilitation arm, or (3) telerehabilitation with pharmacological pain management arm. All patients underwent automated function and pain monitoring with data reporting to their care teams. Participants in arms 2 and 3 received 6 months of centralized telerehabilitation provided by a physical therapist-physician team. Those in arm 3 also received nurse-coordinated pharmacological pain management. MAIN OUTCOMES AND MEASURES Blinded assessment of function using the Activity Measure for Postacute Care computer adaptive test, pain interference and average intensity using the Brief Pain Inventory, and quality of life using the EQ-5D-3L was performed at baseline and months 3 and 6. Hospitalizations and discharges to postacute care facilities were recorded. RESULTS The study included 516 participants (257 women and 259 men; mean [SD] age, 65.6 [11.1] years), with 172 randomized to 1 of 3 arms. Compared with the control group, the telerehabilitation arm 2 had improved function (difference, 1.3; 95% CI, 0.08-2.35; P = .03) and quality of life (difference, 0.04; 95% CI, 0.004-0.071; P = .01), while both telerehabilitation arms 2 and 3 had reduced pain interference (arm 2, −0.

Oncologic emergencies can occur at any time during the course of a malignancy, from the presenting symptom to end-stage disease. Although some of these conditions are related to cancer therapy, they are by no means confined to the period of initial diagnosis and active treatment. In the setting of recurrent malignancy, these events can occur years after the surveillance of a cancer patient has been appropriately transferred from a medical oncologist to a primary care provider. As such, awareness of a patient's cancer history and its possible complications forms an important part of any clinician's knowledge base. Prompt identification of and intervention in these emergencies can prolong survival and improve quality of life, even in the setting of terminal illness. This article reviews hypercalcemia, hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac tamponade, superior vena cava syndrome, neutropenic fever, spinal cord compression, increased intracranial pressure, seizures, hyperviscosity syndrome, leukostasis, and airway obstruction in patients with malignancies. Chemotherapeutic emergencies are also addressed.