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An earlier report documented significant improvement in progression-free survival among patients with metastatic breast cancer treated with fulvestrant and a cyclin-dependent kinase inhibitor, ribociclib. With longer follow-up, it is clear that fulvestrant and ribociclib also prolong overall survival.

Background The phase III EMILIA and TH3RESA trials demonstrated clinical benefits of trastuzumab emtansine (T-DM1) therapy in patients with previously treated HER2-positive metastatic breast cancer (MBC). Data from these and other trials showed that T-DM1–associated survival benefits were observed across biomarker subgroups tested in these trials. Prespecified, exploratory analyses of the phase III MARIANNE study examined the effects of HER2-related biomarkers on PFS in patients administered T-DM1 in the first-line MBC setting. Methods In MARIANNE, patients with previously untreated HER2-positive MBC were randomized (1:1:1) to trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab. Biomarker subgroups included HER2 and HER3 mRNA expression levels (≤median vs. >median), HER2 staining intensity (IHC 3+ vs. 2+ vs. 0/1+), PIK3CA status (mutated vs. non-mutated), PTEN H-score (≤median vs. >median), and PTEN protein expression level (0 vs. 1+ vs. 2+ vs. 3+ vs. 4+). PFS was analyzed descriptively for each subgroup using Kaplan–Meier methodology. Additional exploratory post-hoc analyses evaluated the effects of HER2 heterogeneity. Multivariate analyses were also performed. Results Median PFS was numerically longer for patients with HER2 mRNA levels >median versus ≤median across treatment arms. In general, there were no predictive biomarkers of benefit for either T-DM1 treatment arm; most hazard ratios were close to 1 with wide confidence intervals that included the value 1. Focal HER2 expression (IHC 3+ or IHC 2+) was present in 3.8% of patients and was associated with numerically shorter PFS in the T-DM1–containing treatment arms versus trastuzumab plus taxane. Compared with non-mutated PIK3CA , mutated PIK3CA was associated with numerically shorter median PFS across treatment groups. Post-hoc multivariate analysis showed HER2 mRNA expression and mutated PIK3CA were prognostic for PFS ( P  ≤ 0.001 for both biomarkers). Conclusions In MARIANNE, biomarkers related to the HER2 pathway did not have predictive value for PFS when comparing T-DM1 (with or without pertuzumab) with trastuzumab plus taxane. However, HER2 mRNA level and PIK3CA mutation status showed prognostic value. Evaluation of other potential biomarkers, including immune markers, is ongoing. Trial registration Registration number: NCT01120184 . Date of registration: April 28, 2010 (registered prospectively).

Purpose In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC). Methods Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints. Results The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators. Conclusions The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.

Introduction Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance patient-centered care. We evaluated the feasibility of REMOQOL in the French context in the QOLIBRY study. The primary objective was to assess the patients’ compliance with REMOQOL. Methods The QOLIBRY study was a single-center, prospective study conducted in the University Hospital of Besançon (France). Eligible patients were those treated with systemic therapies for breast, lung or colorectal cancer at any stage. Patients were invited to complete the EORTC QLQ-C30 questionnaire and cancer-site-specific modules before each visit on tablets and/or computers in the hospital or at home. During the consultation, physicians had real-time access to visual summaries of HRQoL scores. Compliance was assessed as adequate if at least 66% of HRQoL assessments were completed during the 4 months of follow-up. Results Between March 2016 and October 2018, 177 patients were included in the QOLIBRY study. Median age was 64 years (IQR 54–71). The proportion of patients with an adequate compliance rate was 95.5% ( n  = 63) in the breast cancer cohort, 98.2% ( n  = 55) in the colorectal cancer cohort, and 90.9% ( n  = 50) in the lung cancer cohort. The physicians checked the HRQoL results in 73.1% of visits and prescribed supportive care and adapted patient management in 8.3% and 5.2% of visits, respectively. Conclusion & perspectives The results of QOLIBRY study suggest that REMOQOL is feasible in the French context. However, information about HRQoL monitoring, training of the physicians in the use of the software, and recommendations for using HRQoL results to guide care are essential and must be improved.

Treatment for triple-negative breast cancers has always been perceived as a “north face” (an allusion to the fact that the north face of a mountain in the northern hemisphere is usually the most formidable and challenging for mountain climbers), and numerous studies have failed to confirm that particular treatments confer a substantial benefit. In this issue of the Journal , Cortes et al. 1 report that pembrolizumab — a breakthrough therapeutic treatment for patients with advanced triple-negative breast cancer — combined with chemotherapy prolonged overall survival among these patients. These results confirm the relationship between programmed death ligand 1 (PD-L1) expression and . . .

Pneumatic transportation systems (PTS) were recently proposed as a method to carry ready-for-injection diluted monoclonal antibodies (mAbs) from the pharmacy to the bedside of patients. This method reduces transportation time and improves the efficiency of drug distribution process. However, mAbs are highly sensitive molecules for which subtle alterations may lead to deleterious clinical effects. These alterations can be caused by various external factors such as temperature, pH, pressure, and mechanical forces that may occur during transportation. Hence, it is essential to ensure that the mAbs transported by PTS remain stable and active throughout the transportation process. This study aims to determine the safety profile of PTS to transport 11 routinely used mAbs in a clinical setting through assessment of critical quality attributes (CQA) and orthogonal analysis. Hence, we performed aggregation/degradation profiling, post-translational modifications identification using complementary mass spectrometry-based methods, along with visible and subvisible particle formation determination by light absorbance and light obscuration analysis. Altogether, these results highlight that PTS can be safely used for this purpose when air is removed from the bags during preparation.

IntroductionOvarian cancer (OC) is the most lethal gynecological cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy appears to increase survival, and normothermic intraperitoneal chemotherapy (IPC) could improve overall survival (OS). Furthermore, intraperitoneal epinephrine could decrease the toxicity of chemotherapy by decreasing the systemic absorption of chemotherapy. The goal of this study was to assess the effects of CRS and IPC with intraperitoneal epinephrine, as first-line therapy, on the survival of patients with serous epithelial OC (EOC) with peritoneal metastases.MethodsA prospective monocentric database was retrospectively searched for all patients with advanced serous EOC treated by interval or consolidative CRS plus IPC with intraperitoneal epinephrine after neoadjuvant chemotherapy. OS and disease-free survival (DFS), postoperative complications, and prognostic factors were analyzed.ResultsFrom January 2003 to December 2017, 124 patients with serous EOC were treated with interval (n = 58) or consolidative (n = 66) complete CRS plus IPC with intraperitoneal epinephrine. The median follow-up was 77.8 months, the median OS was 60.8 months, and the median DFS was 21.2 months. In our multivariate analysis, a higher Peritoneal Cancer Index (PCI) and positive lymph node status resulted in worse OS, while higher World Health Organization score, higher PCI score, and positive lymph node status were risk factors for worse DFS. Grade 3 or higher surgical morbidity occurred in 27.42% of cases; only 3.2% had grade 3 renal toxicity and mortality was 0.8%.ConclusionCRS and IPC with intraperitoneal epinephrine in stage III EOC offer good OS and DFS with acceptable morbidity and mortality rates.

Background and objectiveIn breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion.Patients and methodsA literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose–volume analysis of axillary levels in breast irradiation. The following MESH terms were used: “breast cancer/lymph nodes” AND “radiotherapy dosage.”ResultsThirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using “high tangential” fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively.ConclusionOur literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

Purpose We report the results of a retrospective analysis of the fulvestrant and palbociclib combination within a temporary authorization of use (TAU) program in 77 heavily pretreated patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. Methods All patients who received the fulvestrant and palbociclib combination within this TAU program were included. Toxicities were graded using the CTCAE v5 scale. Results The majority of patients (62.3%) were previously treated with the mTOR inhibitor everolimus. The median number of previous treatments for their metastatic disease was 4. With a median follow-up of 14 months, the median progression-free survival (PFS) was 7.6 months. The median PFS significantly ( p  < 0.0001) decreased with the number of previous treatment lines in the metastatic setting. The median PFS was 5.5 months in patients who had previously progressed on everolimus compared to 9.3 months in the everolimus non-pretreated subgroup. No significant difference in median PFS was detected in patients according to age. The median overall survival rate was not reached. The clinical benefit rate was 64%, including 4% of complete responses, 26% partial responses, and 34% stable diseases for the entire cohort. Conclusions The fulvestrant and palbociclib combination exerts an appreciable effect on metastatic heavily pretreated patients with a tolerable toxicity profile.

Background Endocrine therapy (ET)-based regimens are the mainstay of treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. With the introduction of new treatment classes, it is important to examine patient symptoms and health-related quality of life (HRQoL) at the start of this changing therapeutic landscape. This real-world study describes the patient-reported outcomes (PROs) of women with HR+/HER2− advanced breast cancer receiving ET-based regimens who were naïve to systemic treatment in the advanced setting across five European countries (EU5). Methods Data were collected between March and July 2017 from surveyed oncologists and their patients at a single time point using the multinational Adelphi Advanced Breast Cancer Disease Specific Programme™. Patients completed PRO questionnaires on HRQoL (EORTC QLQ-C30), pain severity and interference, and work and activity impairment. A multiple linear regression model explored factors associated with HRQoL. Results Across EU5, 226 physicians provided data on 781 women with HR+/HER2− advanced breast cancer taking their first ET-based regimen for advanced disease, of whom 252 provided PRO data. This subset had a mean age of 67.1 years, 94% were postmenopausal, 89% were diagnosed with advanced breast cancer at initial presentation, 79% had stage IV disease (66% of these patients had bone metastases and 38% had visceral metastases, including 18% with liver metastases) and 77% were on endocrine-only therapy as their initial treatment for advanced disease. The mean EORTC QLQ-C30 global health score (50.9) was worse than the reference value for patients with advanced breast cancer (60.2). Fatigue, pain, and insomnia were the most severe symptoms, and mean functioning scores were also worse than reference values. “Worst pain” and “pain interference” were moderate/severe for 42 and 80% of patients. Mean activity impairment was 44%, and greater activity impairment was associated with poorer HRQoL. Conclusions Despite receiving first-line ET-based regimens for advanced disease, these women had a poor HRQoL and high levels of symptoms, pain, pain interference and activity impairment. New treatments that maintain a stable disease state and reduce activity impairment may have a positive effect on the HRQoL of those living with advanced breast cancer.