Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03).

PURPOSE: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed. PATIENTS AND METHODS: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS: Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION: At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer.

Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC.

Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention.

Fostering healthcare innovation in public hospitals: the Queensland experience.

Faced with scarce resources and a demand for health care that exceeds supply, health policy makers at all levels of government need to adopt some form of rationing when deciding which health services should be funded in the public health system. With a relatively small investment, programs such as Queensland Health's New Technology Funding Evaluation Program (NTFEP) fosters innovation by providing funding and pilot studies for new and innovative healthcare technologies. The NTFEP assists policy makers to make informed decisions regarding investments in new safe and effective technologies based on available evidence gathered from real-world settings relevant to Queensland patients and clinicians. In addition, the NTFEP allows appropriate patient access, especially in rural and remote locations, to potentially beneficial technologies and acts a gatekeeper, protecting them from technologies that may be detrimental or harmful.

Preoperative taxane-based chemotherapy in a standardized protocol for locally advanced breast cancer.

AIMS: To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) in predicting the extent of residual disease. METHODS: Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m(2) , doxorubicin 50 mg/m(2) , cyclophosphamide 500 mg/m(2) (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate. RESULTS: Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol-specified time and 12 (23%) patients had breast conservation surgery. At a median follow-up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease-free survival. CONCLUSION: This regimen of TAC is effective and well-tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.

To tell or not to tell: the community wants to know about expensive anticancer drugs as a potential treatment option.

PURPOSE: Many new cancer treatments are available only at significant financial cost to the patient. We previously reported that Australian medical oncologists commonly do not discuss unsubsidized, expensive anticancer drugs (EACD) because of concern about causing distress. We argued that this position was not consistent with modern ethical principals but wanted to seek the community viewpoint. METHODS: A cross-sectional telephone survey of the Australian general public was performed. Respondents' views were sought about three hypothetical scenarios in which they were diagnosed with incurable cancer and an EACD treatment (out-of-pocket cost US$25,000) was available. RESULTS: Responses were obtained from 1,255 respondents (response rate, 43%). One hundred thirty-seven (11%) had a prior cancer diagnosis. Ninety-one percent of respondents wanted to be told by their doctor about an EACD that could improve survival by an additional 4 to 6 months, with 51% prepared to pay for it. People were more willing to pay if the drug could improve quality of life (71%) or if there was no effective standard treatment (76%). Sixty-eight percent believed the government should pay. Cost would be a significant financial burden for 31% of those willing to pay. Those more likely to want to be informed were younger, employed, better-educated, or had higher income levels (P < .05). Responses did not vary with the person's personal experience of cancer. Of the 9% who did not wish to be informed, half of these were concerned about the information causing distress. CONCLUSION: The Australian general public wants to be informed about EACD as potential treatment options, even if they are not willing or readily able to pay for them.