Antibiotics and Imiquimod for Cutaneous T-Cell Lymphoma in Veterans: A Patient Population with Agent Orange Exposure

Lessons Learned

• Staphylococcus aureus infection in cutaneous T-cell lymphoma (CTCL) is thought to contribute to disease progression; thus, adjunctive treatment with antibiotics warrants further investigation.
• This trial of antibiotic therapy followed by imiquimod in early stage CTCL was not completed because of difficulties with patient accrual.

     

Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded,Placebo-Controlled,Randomized Phase III Trial (ALTER0703)

Background

Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC.

Materials and Methods

This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1–14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety.

Results

A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4–4.5) over placebo group (1.5 months; 95% CI, 1.4–1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27–0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8–9.7 vs. 7.2 months; 95% CI, 6.2–8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%).

Conclusion

Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients.

Implications for Practice

In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

     

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

     

A Phase I,First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody,in HER3-Expressing Solid Tumors

Background

GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors.

Patients and Methods

Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4–30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly.

Results

Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC).

Conclusion

GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion–positive cancers.

Implications for Practice

This first-in-human study confirms that GSK2849330 is well tolerated. Importantly, across a variety of HER3-expressing advanced tumors, prospective selection by HER3/NRG1 expression alone was insufficient to identify patients who could benefit from treatment with this antibody-dependent cell-mediated cytotoxicity– and complement-dependent cytotoxicity–enhanced anti-HER3 antibody. The only confirmed durable response achieved was in a patient with CD74-NRG1-rearranged lung cancer. This highlights the potential utility of screening for NRG1 fusions prospectively across tumor types to enrich potential responders to anti-HER3 agents in ongoing trials.

     

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer

Background

Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports.

Materials and Methods

Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms.

Results

In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36–3.45) and anxiety (RR, 1.48; 95% CI, 1.05–2.09).

Conclusion

Oncologists frequently underestimate patients’ depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms.

Implications for Practice

In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients’ mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients’ psychological health.

     

Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial

Background

Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision-related outcomes in patients with orbital and extensive periocular BCC (opBCC).

Materials and Methods

In this open-label, nonrandomized phase IV trial, we enrolled patients with globe- and lacrimal drainage system–threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists.

Results

In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1–15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2–4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1–91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins.

Conclusion

Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number.NCT02436408.

Implications for Practice

Use of the antihedgehog inhibitor vismodegib resulted in preservation of end-organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end-organ preservation.

     

Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Background

Immune checkpoint inhibitors (ICIs) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs), and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in patients with mRCC treated with ICIs.

Methods

We performed a retrospective study of 200 patients with mRCC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using Common Terminology Criteria in Adverse Events version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios (ORs) for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate.

Results

Most patients (71.0%) were male, and one-third of patients (33.0%) experienced at least one irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (hazard ratio [HR], 0.52; p = .013), higher chance of CB (OR, 2.10; p = .023) and showed a trend toward longer PFS (HR, 0.71; p = .065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS and PFS and higher chance of CB. In a 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p = .045). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p = .005) and PFS (7.5 vs. 3.6 months, p = .003) without landmark compared with patients who did not.

Conclusion

We found that patients with mRCC treated with ICIs who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared with patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in patients with mRCC treated with ICIs. Future prospective studies are warranted to validate these findings.

Implications for Practice

This study found that early onset immune-related adverse events (irAEs) are associated with significantly improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). In this site-specific irAE analysis, endocrine irAEs, particularly thyroid irAEs, were significantly associated with improved clinical outcomes. These results have implications for practicing medical oncologists given the increasing use of ICIs for the treatment of mRCC. Importantly, these results suggest that early irAEs and thyroid irAEs at any time on treatment with ICIs may be clinical biomarkers of clinical outcomes in patients with mRCC treated with ICIs.

     

The Effect of Concomitant Proton Pump Inhibitor and Cabozantinib on the Outcomes of Patients with Metastatic Renal Cell Carcinoma

Introduction

Cabozantinib is an oral tyrosine kinase inhibitor that is approved for the treatment of metastatic renal cell carcinoma (mRCC). Cabozantinib is a weak base that exhibits a pH-dependent solubility profile in vitro which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPIs). The purpose of this study was to investigate whether PPI use has an impact on the efficacy, safety, and residual concentration (Ctrough) of cabozantinib in patients with mRCC.

Materials and Methods

This is a retrospective review of a prospectively collected electronic database of patients with mRCC who received cabozantinib at Gustave Roussy between February 2014 and December 2018. The Kaplan-Meier method was used for survival analysis and the Cox proportional-hazard model for uni- and multivariate analysis. In parallel, we conducted a pharmacokinetic study of cabozantinib in a distinct cohort of 50 mRCC patients, in which cabozantinib Ctrough was assayed using a validated tandem mass spectrometry–liquid chromatography method.

Results

We identified 99 patients treated with cabozantinib, including 43 patients being PPI users. With a median follow-up of 30.3 months, PPI users showed similar progression-free survival and overall survival outcomes compared with PPI nonusers. Similarly, the incidence of adverse events was not significantly different between the PPI users and nonusers, although PPI users required dose reductions more often. In the independent pharmacokinetic cohort, of whom 21 received PPI concomitantly, Ctrough was similar between the two groups.

Conclusion

In line with the pharmacologic data, the concomitant use of PPI does not significantly impact the efficacy or safety of cabozantinib in patients with mRCC.

Implications for Practice

Drug interactions, especially between targeted therapies and proton pump inhibitors (PPI), were shown to potentially impact the outcomes of cancer patients. Cabozantinib, a current therapeutic standard in metastatic renal cell carcinoma (mRCC), exhibits a pH-dependent solubility profile, which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPI). At the present time, there is no evidence regarding the effect of PPIs on cabozantinib's efficacy and safety in patients with mRCC. This study found that the concomitant use of PPI during cabozantinib treatment in mRCC patients does not appear to impact the residual concentration, efficacy, and safety of cabozantinib in a real-life context.

     

Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial

Lessons Learned

• Administration of autologous invariant natural killer T (iNKT) cells was safe and well-tolerated in patients with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage B/C).
• Expanded iNKT cells produced T-helper 1–like responses with possible antitumor activity.
• No severe adverse events were observed in any of the enrolled patients, including one patient who received 10¹⁰ in vitro–expanded autologous iNKT cells as a single infusion.

     

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study

Background

This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk.

Materials and Methods

The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort.

Results

The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44–4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58–5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results.

Conclusion

A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later.

Implications for Practice

In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

     

Validity and Reliability of the Memorial Delirium Assessment Scale-Thai Version (MDAS-T) for Assessment of Delirium in Palliative Care Patients

Background

Delirium, a neuropsychiatric syndrome that occurs throughout medical illness trajectories, is frequently misdiagnosed. The Memorial Delirium Assessment Scale (MDAS) is a commonly used tool in palliative care (PC) settings. Our objective was to establish and validate the Memorial Delirium Assessment Scale-Thai version (MDAS-T) in PC patients.

Materials and Methods

The MDAS was translated into Thai. Content validity, inter-rater reliability, and internal consistency were explored. The construct validity of the MDAS-T was analyzed using exploratory factor analysis. Instrument testing of the MDAS-T, the Thai version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU-T), and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as the gold standard was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff score. The duration of each assessment was recorded.

Results

The study enrolled 194 patients. The content validity index was 0.97. The intraclass correlation coefficient and Cronbach's α coefficient were 0.98 and 0.96, respectively. A principal component analysis indicated a homogeneous, one-factor structure. The area under the ROC curve was 0.96 (95% confidence interval [CI], 0.93–0.99). The best combination of sensitivity and specificity (95% CI) of the MDAS-T were 0.92 (0.85–0.96) and 0.90 (0.82–0.94), respectively, with a cutoff score of 9, whereas the CAM-ICU-T yielded 0.58 (0.48–0.67) and 0.98 (0.93–0.99), respectively. The median MDAS-T assessment time was 5 minutes.

Conclusion

This study established and validated the MDAS-T as a good and feasible tool for delirium screening and severity rating in PC settings.

Implications for Practice

Delirium is prevalent in palliative care (PC) settings and causes distress to patients and families, thereby making delirium screening necessary. This study found that the MDAS-T is a highly objective and feasible test for delirium screening and severity monitoring in PC settings and can greatly improve the quality of care for this population.

     

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study

Lessons Learned

• Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity.
• This combination might represent a treatment option for refractory metastatic colorectal cancer.

     

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer

Lessons Learned

• Antitumor activity was observed in the study population.
• Dose modifications of cabozantinib improve long-term tolerability.
• Biomarkers are needed to identify patient populations most likely to benefit.
• Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted.

     

A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26–104/RFASE in Patients with Advanced Solid Malignancies

Lessons Learned

• The novel therapeutic vaccine hVEGF_26–104/RFASE was found to be safe and well tolerated in patients with cancer.
• hVEGF_26–104/RFASE failed to induce seroconversion against native hVEGF₁₆₅ and, accordingly, neither a decrease in circulating vascular endothelial growth factor (VEGF) levels nor clinical benefit was observed.
• Remarkably, hVEGF_26–104/RFASE induced VEGF₁₆₅-neutralizing antibodies in a nonhuman primate model. The absence of seroconversion in human calls for caution in the interpretation of efficacy of human vaccines in nonhuman primates.

     

Health-Related Quality of Life in Patients with Breast Cancer in Latin America and the Caribbean: A Systematic Review and Meta-Analysis

Background and Objectives

Breast cancer (BC) is the most common cancer in women. It imposes a huge disease burden and a significant impact on health-related quality of life (HRQoL). Our study focused on HRQoL of patients with BC in Latin America and the Caribbean (LAC). We conducted a systematic review to identify relevant articles published between 2008 and August 2018. We conducted several meta-analyses and subgroup analyses by country, disease stage, and instrument used (Prospective Register Of Systematic Reviews registration number: CRD42018106835).

Results

From 2,265 initial references, we finally included 75 articles (8,806 participants) that assessed HRQoL. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 and B23 modules (34 studies; 8 countries; 4,866 participants) were the most used instruments, followed by the Short Form 36-item, the abbreviated version of the World Health Organization Quality of Life instrument, and the Functional Assessment of Cancer Therapy – Breast instrument. Only four studies reported specific HRQoL data of patients with metastatic disease. Half the studies were rated as having moderate quality (38/75), and 38% (29/75) as high quality. We identified substantial heterogeneity. As expected, the meta-analyses revealed that patients with metastatic disease reported lower HRQoL values and high symptom burden compared with patients at earlier stages. Similar results can be observed when we compared patients with early breast cancer in active treatment phases versus those in follow-up.

Conclusion

This study provides a synthesis of breast cancer HRQoL reported in LAC and exposes existing evidence gaps. Patients with BC in active treatment or with metastatic disease had worse HRQoL compared with survivors during the follow-up period.

Implications for Practice

This systematic review provides an exhaustive synthesis of breast cancer health-related quality of life in women in the Latin American and Caribbean region. Patients with breast cancer in active treatment or with metastatic disease had worse health-related quality of life compared with survivors during the different follow-up periods. This study also shows important evidence and methods gaps that can help inform future research.

     

Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen

Lessons Learned

• The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen.
• A comparison with calcium levofolinate (Ca-Lev) showed a similar toxicity profile. The advantages of Na-Lev over Ca-Lev might be the faster drug preparation and the shorter time of drug administration.

     

Prognostic Factors for Overall Survival in Patients with Hormone Receptor-Positive Advanced Breast Cancer: Analyses From PALOMA-3

Background

This analysis investigated whether baseline characteristics affect the survival benefit derived from palbociclib-fulvestrant and the optimal timing of cyclin-dependent kinase 4/6 inhibitor therapy for advanced breast cancer (ABC) in patients from PALOMA-3.

Patients and Methods

In total, 521 patients were randomized 2:1 to receive palbociclib (125 mg/day, 3/1 schedule)–fulvestrant (500 mg, intramuscular injection, on days 1 and 15 of cycle 1, and then day 1 of each subsequent cycle) or matching placebo-fulvestrant. Median overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method.

Results

Multivariable analysis identified endocrine sensitivity, nonvisceral disease, no prior chemotherapy for ABC, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 as significant prognostic factors for OS. Patients without chemotherapy for ABC had fewer prior lines of treatment in any setting and in the ABC setting versus patients with prior chemotherapy for ABC (two or fewer prior systemic therapies: 69% vs. 42%; no more than one prior line for ABC: 82% vs. 33%, respectively). Median OS was prolonged with palbociclib-fulvestrant in patients without prior chemotherapy for ABC (39.7 vs. 29.5 months; hazard ratio, 0.75; 95% confidence interval [CI]: 0.56–1.01) and was similar in patients with prior chemotherapy for ABC (25.6 vs. 26.2 months; hazard ratio, 0.91 [95% CI: 0.63–1.32]) versus placebo-fulvestrant.

Conclusion

Prognostic factors for OS included endocrine sensitivity, nonvisceral disease, ECOG PS of 0, and no prior chemotherapy for ABC. Exploratory analyses suggest improved OS with palbociclib-fulvestrant versus placebo-fulvestrant in patients with no prior chemotherapy for ABC, prior endocrine sensitivity, and fewer prior regimens of systemic therapy. (Clinical trial identification number: NCT01942135).

Implications for Practice

Prognostic factors for overall survival in HR+/HER2− advanced breast cancer (ABC) include the absence of prior chemotherapy in the advanced setting, endocrine sensitivity, nonvisceral disease, and an ECOG performance status of 0. Improved overall survival benefit was observed with palbociclib-fulvestrant versus placebo-fulvestrant in patients (regardless of menopausal status or visceral involvement) with no prior chemotherapy for ABC, with prior endocrine sensitivity, and fewer prior regimens of systemic therapy. Progression-free survival was prolonged with palbociclib across subgroups (regardless of chemotherapy exposure in ABC). These exploratory findings suggest that patients may receive greater clinical benefit from palbociclib-fulvestrant if they receive the combination before chemotherapy in the advanced setting.