Clinical characteristics, treatment patterns, and outcomes in adult patients with germline BRCA1/2-mutated, HER2-negative advanced breast cancer: a retrospective medical record review in the United States.

Aim: To examine clinical characteristics, real-world treatment patterns, and health outcomes among patients with germline BRCA1/2-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). Methods: A retrospective analysis was conducted using medical records from patients with HER2-negative ABC with BRCA1/2 mutation who received cytotoxic chemotherapy. Data were stratified into groups with triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2-negative diagnoses. Time-to-event outcomes (i.e., real-world progression-free survival [rwPFS] and overall survival [OS]) were calculated to summarize health outcomes. Results: When diagnosed with ABC, most patients were younger than 60 years (mean age = 57.3 years), were white (76.4%), and had a family history of BRCA-related cancer (71.5%). A total of 305 patient records were examined; 194 patients (63.6%) had advanced TNBC, and 111 patients (36.4%) had HR+/HER2-negative ABC. Chemotherapy was primarily used as first-line treatment for both subgroups, but the TNBC subgroup received poly (ADP-ribose) polymerase (PARP) inhibitors at triple the rate as a second-line treatment and double the rate as a third-line treatment compared with the HR+/HER2-negative subgroup. Two-year OS rates were similar between the TNBC (73.9%) and the HR+/HER2-negative subgroups (77.0%), and anemia, nausea, and neutropenia were the most commonly reported toxicities across all treatments. Conclusion: Clinicians should consider the use of targeted agents such as PARP inhibitors in earlier lines of therapy for ABC given the growing evidence that PARP inhibitors may improve PFS compared with chemotherapy while potentially offering a more manageable toxicity profile and improved quality of life.

Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer.

This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).

Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations.

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

TALAPRO-3 clinical trial protocol: phase III study of talazoparib plus enzalutamide in metastatic castration-sensitive prostate cancer.

Poly(ADP-ribose) polymerase inhibitors in combination with androgen-receptor signaling inhibitors are a promising therapeutic option for patients with metastatic castration-sensitive prostate cancer (mCSPC) and homologous recombination repair (HRR) gene alterations. Here, we describe the design and rationale of the multinational, phase III, TALAPRO-3 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide in patients with mCSPC and HRR gene alterations. The primary end point is investigator-assessed radiographic progression-free survival (rPFS) per RECIST 1.1 in soft tissue, or per PCWG3 criteria in bone. The TALAPRO-3 study will demonstrate whether the addition of talazoparib can improve the efficacy of enzalutamide as assessed by rPFS in patients with mCSPC and HRR gene alterations undergoing androgen deprivation therapy. Clinical Trial Registration:NCT04821622 (ClinicalTrials.gov) Registry Name: Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC. Date of Registration: 29 March 2021.

The impact of race on survival in metastatic prostate cancer: a systematic literature review.

BACKGROUND: Prostate cancer (PC) is the second most diagnosed cancer in men worldwide. While racial and ethnic differences exist in incidence and mortality, increasing data suggest outcomes by race among men with newly diagnosed PC are similar. However, outcomes among races beyond Black/White have been poorly studied. Moreover, whether outcomes differ by race among men who all have metastatic PC (mPC) is unclear. This systematic literature review (SLR) provides a comprehensive synthesis of current evidence relating race to survival in mPC. METHODS: An SLR was conducted and reported in accordance with PRISMA guidelines. MEDLINE®, Embase, and Cochrane Library using the Ovid® interface were searched for real-world studies published from January 2012 to July 2022 investigating the impact of race on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with mPC. A supplemental search of key congresses was also conducted. Studies were appraised for risk of bias. RESULTS: Of 3228 unique records identified, 62 records (47 full-text and 15 conference abstracts), corresponding to 54 unique studies (51 United States and 3 ex-United States) reporting on race and survival were included. While most studies showed no difference between Black vs White patients for OS (n = 21/27) or PCSM (n = 8/9), most showed that Black patients demonstrated improved OS on certain mPC treatments (n = 7/10). Most studies found no survival difference between White patients and Hispanic (OS: n = 6/8; PCSM: n = 5/6) or American Indian/Alaskan Native (AI/AN) (OS: n = 2/3; PCSM: n = 5/5). Most studies found Asian patients had improved OS (n = 3/4) and PCSM (n = 6/6) vs White patients. CONCLUSIONS: Most studies found Black, Hispanic, and AI/AN patients with mPC had similar survival as White patients, while Black patients on certain therapies and Asian patients showed improved survival. Future studies are needed to understand what aspects of race including social determinants of health are driving these findings.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

BACKGROUND: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. PATIENTS AND METHODS: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed. RESULTS: Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose). CONCLUSIONS: Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated. CLINICALTRIALS.GOV IDENTIFIER: NCT03499353.

Real-World Treatment Patterns Among Patients With Metastatic Castration-Resistant Prostate Cancer: Results From an International Study.

BACKGROUND: There is limited real-world evidence on how increasing use of treatment intensification in metastatic castration-sensitive prostate cancer (mCSPC) has influenced treatment decisions in metastatic castration-resistant prostate cancer (mCRPC). The study objective was to evaluate the impact of novel hormonal therapy (NHT) and docetaxel use in mCSPC on first-line treatment patterns among patients with mCRPC in 5 European countries and the United States (US). METHODS: Physician-reported data on patients with mCRPC from the Adelphi Prostate Cancer Disease Specific Program were descriptively analyzed. RESULTS: A total of 215 physicians provided data on 722 patients with mCRPC. Across 5 European countries and the US, 65% and 75% of patients, respectively, received NHT, and 28% and 9% of patients, respectively, received taxane chemotherapy as first-line mCRPC treatment. In Europe, patients who had received NHT in mCSPC (n = 76) mostly received taxane chemotherapy in mCRPC (55%). Patients who had received taxane chemotherapy, or who did not receive taxane chemotherapy or NHT in mCSPC (n = 98 and 434, respectively) mostly received NHT in mCRPC (62% and 73%, respectively). In the US, patients who had received NHT, taxane chemotherapy, or neither in mCSPC (n = 32, 12, and 72, respectively) mostly received NHT in mCRPC (53%, 83%, and 83%, respectively). Two patients in Europe were rechallenged with the same NHT. CONCLUSIONS: These findings suggest that physicians consider mCSPC treatment history when making first-line treatment decisions in mCRPC. Further studies are needed to better understand optimal treatment sequencing, especially as new treatments emerge.

Real-World Treatment Trends Among Patients with Metastatic Castration-Sensitive Prostate Cancer: Results from an International Study.

BACKGROUND: Continuous androgen deprivation therapy ± first-generation non-steroidal antiandrogen was previously the standard-of-care for patients with metastatic castration-sensitive prostate cancer (mCSPC). Treatment intensification with novel hormonal therapy (NHT) or taxane chemotherapy is now approved and guideline-recommended for these patients. METHODS: Physician-reported data on adult patients with mCSPC from the Adelphi Prostate Cancer Disease Specific Programme were analyzed descriptively. We evaluated real-world treatment trends for patients with mCSPC in 5 European countries (United Kingdom, France, Germany, Spain, and Italy) and the United States (US), looking at differences between patients initiating treatment in 2016-2018 and in 2019-2020. We also investigated treatment trends by ethnicity and insurance status in the US. RESULTS: This study found that most patients with mCSPC do not receive treatment intensification. However, greater use of treatment intensification with NHT and taxane chemotherapy was observed in 2019-2020 than in 2016-2018 across 5 European countries. In the US, greater use of treatment intensification with NHT in 2019-2020 than in 2016-2018 was observed for all ethnicity groups and those with Medicare and commercial insurance status. CONCLUSIONS: As the number of patients with mCSPC who receive treatment intensification increases, more patients who progress to metastatic castration-resistant prostate cancer (mCRPC) will have been exposed to intensified treatments. Treatment options for patients with mCSPC and mCRPC overlap, suggesting that an unmet need will emerge for new therapies. Further studies are needed to understand optimal treatment sequencing in mCSPC and mCRPC.

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer.

BACKGROUND: Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting. PATIENTS AND METHODS: Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics. RESULTS: Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality. CONCLUSION: Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA.

Real-World Study of Regional Differences in Patient Demographics, Clinical Characteristics, and BRCA1/2 Mutation Testing in Patients with Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer in the United States, Europe, and Israel.

INTRODUCTION: Genetic mutations in breast cancer susceptibility gene 1 or 2 (BRCA1/2) confer a high risk for developing breast cancer; however, at least 50% of women with BRCA1/2 mutations go undiagnosed. This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2 mutation testing in the USA, European Union (EU4), and Israel in a real-world population of patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS: This study was a retrospective analysis of data from the Adelphi Real World ABC Disease Specific Programme in the USA, EU4, and Israel. Medical oncologists completed a patient record form, which included detailed questions on demographics, clinical assessments and outcomes, and treatment history. Eligible patients were at least 18 years of age and receiving therapy for stage IIIb-IV ABC. RESULTS: Among the 2527 study patients, 407 were from the USA, 1926 were from the EU4, and 194 were from Israel; 86% had hormone receptor-positive (HR+)/HER2- ABC and 14% had triple-negative breast cancer (TNBC). Israeli patients had a higher rate of family history of BRCA-related cancer (69%) compared with patients in the EU4 (18%; p < 0.0001) and USA (18%; p < 0.0001). Among patients with HR+/HER2- ABC, the BRCA1/2 testing rate was 99% in Israel, 37% in the EU4, and 68% in the USA (p < 0.0001 vs Israel and the EU4). The age of tested patients was significantly younger in Israel (56 years) compared with the EU4 (59 years; p = 0.016 vs Israel) and USA (64 years; p < 0.0001 vs Israel and the EU4). Among patients with TNBC, the BRCA1/2 testing rate was 100% in Israel, 78% in the EU4 (p < 0.0001 vs Israel), and 93% in the USA (p < 0.002 vs the EU4). Among tested patients, genetic counseling rates were also higher in Israel (98%) compared with the EU4 (40%; p < 0.0001) and USA (38%; p < 0.0001). CONCLUSIONS: Testing and genetic counseling rates for BRCA1/2 mutations were very high in Israel, potentially due to the high rate of family history of BRCA-related cancer in this population and higher general awareness of genetic testing. In the EU4 and USA, overall rates of testing for BRCA1/2 mutations and genetic counseling were significantly lower compared with Israel. Given the high risk of breast cancer in BRCA1/2 mutation carriers and the efficacy of new therapies in treating ABC with a BRCA1/2 mutation, efforts should be made to improve BRCA1/2 testing rates in Europe and the USA.

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1.

BACKGROUND: Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations. OBJECTIVE: To evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. DESIGN, SETTING, AND PARTICIPANTS: TALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Men completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory-Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations. RESULTS AND LIMITATIONS: In the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (-1.08 [-1.52, -0.65]) and the BRCA1/2 subset (-1.15 [-1.67, -0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset. CONCLUSIONS: In heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high. PATIENT SUMMARY: We show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.

Real-world patient-reported outcomes and physician satisfaction with poly (ADP-ribose) polymerase inhibitors versus chemotherapy in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative advanced breast cancer from the United States, Europe, and Israel.

BACKGROUND: In clinical trials, poly (ADP-ribose) polymerase inhibitors (PARPi) versus chemotherapy resulted in significantly improved progression-free survival, manageable adverse event profiles, and favorable patient-reported outcomes (PROs) in patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) and germline BRCA1/2 mutations (gBRCA1/2mut). The objective of this study was to evaluate PROs and physician satisfaction with treatment in patients with gBRCA1/2mut HER2- ABC receiving PARPi or physician's choice of chemotherapy in a multi-country, real-world setting. METHODS: This retrospective analysis used data from the Adelphi Real World ABC Disease Specific Programmes in the United States, European Union, and Israel. PROs were assessed at a single timepoint using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) scale, Cancer Therapy Satisfaction Questionnaire (CTSQ), and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) and the breast cancer-specific module (QLQ-BR23). Baseline PROs were not assessed. Physician satisfaction with treatment scores was dichotomized to a 0/1 variable (0 = very dissatisfied/dissatisfied/moderately satisfied; 1 = satisfied/very satisfied). Scores were compared using inverse-probability-weighted regression adjustment, controlling for multiple confounding factors. RESULTS: The study included 96 patients (PARPi, n = 38; platinum/non-platinum-based chemotherapy, n = 58). Patients receiving PARPi versus chemotherapy reported significantly better scores on the EQ-5D-5L Health Utility Index. On the EORTC QLQ-C30 functional scales, patients receiving PARPi reported significantly better scores (mean ± SE) for physical functioning (80.0 ± 2.4 vs 71.9 ± 3.4; p < 0.05) and social functioning (82.0 ± 6.2 vs 63.6 ± 3.7; p < 0.05) and, on the symptom scales, reported significantly better scores for constipation (1.9 ± 1.8 vs 18.7 ± 3.2; p < 0.001), breast symptoms (0.4 ± 3.9 vs 13.3 ± 2.6; p < 0.01), arm symptoms (2.6 ± 1.3 vs 11.4 ± 2.4; p = 0.001), and systemic therapy side effects (13.5 ± 1.8 vs 29.4 ± 2.3; p < 0.001). In contrast, patients receiving chemotherapy scored significantly better on the nausea/vomiting scale (18.3 ± 2.8 vs 34.5 ± 5.1; p < 0.01). Patients receiving PARPi reported numerically better satisfaction scores on the CTSQ scales. Physicians were more likely to be satisfied/very satisfied with PARPi versus chemotherapy (95.4% ± 7.3% vs 40.8% ± 6.2%; p < 0.001). CONCLUSIONS: The PRO findings in this real-world population of patients with gBRCA1/2mut HER2- ABC complement those from the pivotal clinical trials, providing further support for treatment with PARPi in these patients.

Real-world study of patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2‒Negative advanced breast cancer: Patient demographics, treatment patterns, adverse events, and physician-reported satisfaction in the United States, Europe, and Israel.

BACKGROUND: Current guidelines for the treatment of human epidermal growth factor receptor 2‒negative (HER2-) advanced breast cancer (ABC) are informed by tumor characteristics and include platinum- and non-platinum-based chemotherapy, chemotherapy plus immunotherapy, endocrine monotherapy, or endocrine therapy plus a targeted therapy. In addition, poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have recently demonstrated improved clinical and patient-reported outcomes and manageable toxicity profiles compared with chemotherapy in patients with germline breast cancer susceptibility gene 1 or 2 (gBRCA1/2)‒mutated HER2- ABC in clinical trials and are now approved to treat this patient population. This study provides complementary real-world data regarding treatment patterns, adverse events, and physician-reported treatment satisfaction in this population. METHODS: This retrospective analysis using the Adelphi Real World ABC Disease Specific Programme in the United States, European Union, and Israel included patients aged ≥18 years receiving therapy for stage IIIb or IV gBRCA1/2-mutated HER2- ABC. Oncologists completed a patient record form detailing patient demographics, clinical assessments, and treatment history and a survey regarding their use of and satisfaction with treatments. RESULTS: Among the 543 patients, mean age was 55 years, 25% were premenopausal, 70% had hormone receptor‒positive (HR+) ABC, and 30% had triple-negative breast cancer (TNBC). PARPi were used in 5%, 11%, and 12% of first-line, second-line, and third-line therapies, respectively, for patients with HR+ ABC; for TNBC, percentages were 18%, 44%, and 36%. Across treatment lines, neutropenia, anemia, and nausea occurred in 16%, 24%, and 32% of patients receiving PARPi, respectively; 22%, 38%, and 33% of patients receiving platinum chemotherapy; and 20%, 20%, and 33% of patients receiving non-platinum-based chemotherapy. Physician satisfaction was highest with PARPi and with chemotherapy plus immunotherapy. CONCLUSIONS: Findings in this real-world population complement clinical trial observations and provide further support for treatment of patients with PARPi in gBRCA1/2-mutated HER2- ABC.

BRCA1/2 Mutation Testing in Patients with HER2-Negative Advanced Breast Cancer: Real-World Data from the United States, Europe, and Israel.

Poly(adenosine diphosphate-ribose) polymerase inhibitors are approved to treat patients harboring a germline breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) with human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC). This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2mut testing within the United States (US), European Union 4 (EU4; France, Germany, Italy, and Spain), and Israel in a real-world population of patients with HER2− ABC. Oncologists provided chart data from eligible patients from October 2019 through March 2020. In the US, EU4, and Israel, 73%, 42%, and 99% of patients were tested for BRCA1/2mut, respectively. In the US and the EU4, patients who were not tested versus tested for BRCA1/2mut were more likely to have hormone receptor­positive (HR+)/HER2− ABC (US, 94% vs. 74%, p < 0.001; EU4, 96% vs. 78%, p < 0.001), less likely to have a known family history of BRCA1/2-related cancer (US, 6% vs. 19%, p = 0.002; EU4, 10% vs. 28%, p < 0.001), and were older (US, 68.9 vs. 62.5 years, p < 0.001; EU4, 66.7 vs. 58.0 years, p < 0.001). Among tested patients, genetic counseling was received by 45%, 53%, and 98% with triple-negative breast cancer, and 36%, 36%, and 98% with HR+/HER2− ABC in the US, EU4, and Israel, respectively. Efforts should be made to improve BRCA1/2 testing rates in the US and Europe.

Awareness and Availability of Routine Germline BRCA1/2 Mutation Testing in Patients with Advanced Breast Cancer in Germany.

Introduction: Diagnostic testing of germline mutations in breast cancer susceptibility genes 1 or 2 (gBRCA1/2) in patients with human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC; locally advanced or metastatic breast cancer) is necessary to assess eligibility for poly(ADP-ribose) polymerase inhibitors (PARPi). We investigated awareness, clinical practice, and the availability of gBRCA1/2 mutation testing in the German outpatient oncology setting. Methods: Office-based oncologists completed a 23-item online survey. Responses were evaluated collectively and by center type. Results: Of 50 oncologists, 33 and 17 were medical and gynecological oncologists, respectively. Oncologists treated a median of 65 (range 14-350) patients with ABC per year. The strongest decision factors to initiate gBRCA1/2 mutation testing were: patient's known family history of gBRCA1/2 mutation-related cancer(s), guideline recommendations, and triple-negative breast cancer (TNBC). In routine practice, 86% of oncologists tested for gBRCA1/2 mutations. Most oncologists (76-98%) reported testing patients with a known family history of gBRCA1/2 mutation-related cancer(s) irrespective of receptor status. For unknown family history, 92% of oncologists reported testing patients with advanced TNBC versus 30% for HR+/HER2- ABC. Oncologists (66%) rated the awareness of therapeutic relevance of gBRCA1/2 mutation testing for targeted treatment selection as good to satisfactory; 22% rated awareness as poor to in-sufficient. Conclusion: Diagnostic gBRCA1/2 mutation testing in patients with HER2- ABC is available and routinely performed in Germany's outpatient oncology setting. However, specific patient subgroups were not routinely tested despite therapeutic indications. Given PARPi availability, opportunities exist to improve testing rates especially for patients with HR+/HER2- ABC without a known family history of gBRCA1/2 mutation-related cancer(s).

Real-world multi-country study of BRCA1/2 mutation testing among adult women with HER2-negative advanced breast cancer.

Aim: We assessed real-world patient demographics and BRCA1/2 mutation testing rates among adult women with HER2-negative advanced breast cancer (ABC). Methods: Oncologists across the USA and in France, Germany, Italy, Spain and the UK provided medical chart data in 2015 and 2017. Results: Overall, 28% of patients received BRCA1/2 mutation testing. Untested patients were more likely to be aged ≥45 years, have hormone receptor-positive/HER2-negative ABC and have no known family history of breast/ovarian cancer. BRCA1/2 mutation testing rates were significantly lower in the European countries, women aged ≥45 years, women without a known family history of breast/ovarian cancer, and women with hormone receptor-positive/HER2-negative ABC versus advanced triple-negative breast cancer. Conclusion: BRCA1/2 mutation testing rates were low, and disparities were observed in patient characteristics among BRCA1/2 mutation-tested versus untested patients.

This study investigated the use of BRCA1/2 genetic testing in women with breast cancer in the USA and Europe. This is important, as mutations in this gene are known to influence cancer progression, with many treatments now available for patients with these mutations. Doctors collected data from patient medical records in both 2015 and 2017. The results show the BRCA1/2 testing rates were low, with only 28% of patients tested. Patients who did not have a test were older, had hormone receptor-positive/HER2-negative cancer and did not have a family history of cancer. Testing rates were also lower in Europe than in the USA. Improved BRCA1/2 testing rates could identify patients at risk and aid physicians and their patients in their choice of treatment, improving outcomes.

Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015-2020.

Real-world evidence (RWE) has garnered great interest to support registration of new therapies and label expansions by the United States Food and Drug Administration (FDA). Currently, practical insights on the design and analysis of regulatory-grade RWE are lacking. This study aimed to analyze attributes of real-world studies in FDA's decision-making and characteristics of full versus accelerated approvals through a systematic review of oncology product approvals. Oncology approvals from 2015 to 2020 were reviewed from FDA.gov. Applications were screened for inclusion of RWE, and variables related to regulatory designations of the application, pivotal clinical trial, and real-world studies were extracted. FDA feedback was reviewed to identify takeaways and best practices for adequate RWE. Among 133 original and 573 supplemental approvals for oncology, 11 and 2, respectively, included RWE; none predated 2017. All real-world studies were retrospective in nature; the most common data source was chart review, and the most common primary endpoint was overall response rate, as in the pivotal trial. The FDA critiqued the lack of the following: a prespecified study protocol, inclusion/exclusion criteria matching to the trial, comparability of endpoint definitions, methods to minimize confounding and address unmeasured confounding, and plans to handle missing data. All full (versus accelerated) approvals shared the following characteristics: high magnitude of efficacy in the pivotal trial; designations of orphan disease, breakthrough therapy, and priority review; and no advisory committee meeting held. This study found that findings from external control real-world studies complemented efficacy data from single-arm trials in successful oncology product approvals.

Payer perceptions on the use of patient-reported outcomes in oncology decision making.

BACKGROUND: In oncology, especially with accelerated regulatory approvals and niche populations, US payers appreciate all evidence that can help support formulary decision making, including evidence beyond traditional safety and efficacy data from clinical trials. Research suggests payers incorporate patient-reported outcome (PRO) evidence in their decision making and expect the importance of PRO evidence to grow. Greater understanding on payers' use of PRO information in oncology is needed. OBJECTIVE: To assess US payer perceptions regarding the use of PRO evidence in informing oncology formulary decision making. METHODS: A multidisciplinary steering committee involving a measurement specialist, health economics and outcomes research experts, and payers developed a survey containing single-answer, multiple-answer, and free-response questions. The pilot survey was tested at a mini-advisory board with 5 US payers and revised based on feedback. In February 2020, the survey was distributed to 221 US payers through the AMCP Market Insights program and 10 additional payer panelists who were invited to discuss and contextualize the survey results. Results were presented primarily as frequencies of responses and evaluated by plan size, type of health plan, and geography (regional vs national). Differences in categorical data responses were compared using Pearson chi-square or Fisher exact tests. Two-tailed values are reported and a P value less than or equal to 0.05 was used to indicate statistical significance. RESULTS: Overall, 106 of 231 payers (45.9%) completed the survey; 45.5% represented small plans (< 1 million lives), and 54.5% represented large plans (≥ 1 million lives). Respondents were largely pharmacists (89.9%), with 55.6% of all respondents indicating their job was pharmacy administrator. The majority of payers (60.0% of small health plans and 57.8% of large plans) felt PRO evidence from clinical trials is useful. Similarly, the majority of payers (57.8% of small plans and 51.9% of large plans) felt PRO evidence from real-world studies is useful. Almost half (47.1%) suggested formulary review would be influenced by a lack of PRO evidence from oncology clinical trials either somewhat, much, or a great deal. Most payers (78.2%) thought PRO evidence is useful for providing additional context for safety of oncology therapies. More than one-third of payers (34.3%) valued PRO evidence when comparing 2 similar therapies, and 51.5% felt PRO evidence may help in measuring value for value-based agreements. Panelists indicated PRO evidence can be useful for developing treatment pathways for addressing health-related quality of life, informing provider-patient dialogues, and defining progression-free survival length and quality. CONCLUSIONS: US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models. Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers. DISCLOSURES: Pfizer provided funding for this research, and employees of Pfizer contributed to the development of the survey instrument, were involved in the interpretation of the data, and contributed to the discussion and output as authors. Biskupiak, Oderda, and Brixner are managers of Millcreek Outcomes Group and were paid as consultants on this project. Burgoyne was a consultant for Pfizer on this project. Arondekar, Deal, and Niyazov are employees of Pfizer and own Pfizer stock. Qwek was an employee of Pfizer at the time of this project and owns Pfizer stock.

Treatment Patterns, Safety, and Patient Reported Outcomes among Adult Women with Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer with or without, or with Unknown, BRCA1/2 Mutation(s): Results of a Real-World Study from the United States, United Kingdom, and four EU Countries.

Introduction: This real-world study assessed the breast cancer susceptibility gene 1 or 2 mutation (BRCA1/2mut) status on treatment patterns, safety, and patient-reported outcomes (PROs) in women with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the USA, the UK, and EU4 countries. Methods: Oncologists abstracted data from medical charts of adult women who presented with HER2- ABC from February to May 2015 and from March to July 2017. Data were collected using a physician-reported form and a patient-reported form, which included questions on breast cancer history/treatment and questions from PRO instruments (EuroQol 5-Dimensions 3-Levels [EQ-5D-3L], Brief Pain Inventory [BPI], European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core 30 and its breast cancer module). Results: In total, 742 oncologists provided data for 6,161 patients; 27.5% were tested for BRCA1/2mut. Out of the total patient population, 3.8% had BRCA1/2mut, 16.6% BRCA1/2 wild-type (BRCA1/2wt), and 79.5% were BRCA1/2 unknown (BRCA1/2unk). Hormone receptor-positive (HR+)/HER2- ABC was more frequent within the BRCA1/2wt versus BRCA1/2mut group and triple-negative breast cancer (TNBC) within the BRCA1/2mut versus BRCA1/2wt group. More patients with HR+/HER2- ABC with BRCA1/2mut received chemotherapy (with or without targeted or endocrine therapy) versus BRCA1/2wt (66.0% vs. 50.4%; p < 0.01); more patients had ≥1 AE (58.0% vs. 39.1%; p < 0.001). Among patients with BRCA1/2mut versus BRCA1/2wt, a significantly higher proportion had some problems or worse pain discomfort (p = 0.021) and anxiety/depression (p = 0.007) as measured by the EQ-5D-3L; role functioning (p < 0.01) and dyspnea (p < 0.05) measured by EORTC were worse with BRCA1/2mut. Pain scores by BPI were similar between groups. Conclusions: In patients with HER2- ABC in the real-world setting, more patients with BRCA1/2mut had TNBC; received chemotherapy; had >1 AE; and experienced increased discomfort, anxiety, and dyspnea and diminished role functioning versus patients with BRCA1/2wt.