Overall Survival Hazard Ratio Research Articles

Bellmunt risk score as a survival predictor in patients with metastatic castration-resistant prostate cancer.

The prognosis of metastatic castration-resistant prostate cancer (mCRPC) is influenced by numerous individual factors. Despite various proposed prognostic models, the clinical application of these remains limited, probably due to complexity. Our study aimed to evaluate the predictive value of the Bellmunt risk score, which is well-known for urothelial carcinoma and easily assessed, in mCRPC patients. The Bellmunt risk score was calculated from three risk factors (Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥1, serum hemoglobin <10 g/dL, presence of liver metastases) in 125 patients who received first-line mCRPC treatment between 2005 and 2023. In addition, a modified score was established (one point each for hemoglobin <10 g/dL and the presence of liver metastases added to the ECOG PS). Associations with overall survival (OS) under first- and second-line therapy were tested using Cox regression analyzes, log-rank tests, concordance index (C-index) and time-dependent receiver operating characteristic. There is a significant correlation between the level of the Bellmunt risk score and shorter OS (hazard ratio: 3.23, 95% confidence interval: 2.06-5.05; log-rank p < 0.001; C-index: 0.724). The semi-quantitative modified risk score showed even better prognostic discrimination (log-rank p < 0.001, C-index: 0.764). The score and its dynamics were also predictive in the second-line setting (log-rank p < 0.001 and = 0.01; C-index: 0.742 and 0.595). The Bellmunt risk score is easy to assess and provides useful prognostic information in mCRPC, and can support physicians in their treatment decisions.

Prediction of ovarian cancer prognosis using statistical radiomic features of ultrasound images.

Ovarian cancer is the deadliest gynecologic malignancy worldwide. Ultrasound is the most useful non-invasive test for preoperative diagnosis of ovarian cancer. In this study, by leveraging multiple ultrasound images from the same patient to generate personalized, informative statistical radiomic features, we aimed to develop improved ultrasound image-based prognostic models for ovarian cancer. A total of 2,057 ultrasound images from 514 ovarian cancer patients, including 355 patients with epithelial ovarian cancer, from two hospitals in China were collected for this study. The models were constructed using our recently developed Frequency Appearance in Multiple Univariate pre-Screening (FAMUS) feature selection algorithm and Cox proportional hazards model. The models showed high predictive performance for overall survival (OS) and recurrence-free survival (RFS) in both epithelial and nonepithelial ovarian cancer, with concordance indices (C-index) ranging from 0.773 to 0.794. Radiomic scores predicted 2-year OS and RFS risk groups with significant survival differences (log-rank test, P<1.0e-4 for both validation cohorts). OS and RFS hazard ratios between low- and high-risk groups were 15.994 and 30.692 (internal cohort) and 19.339 and 19.760 (external cohort), respectively. The improved performance of these newly developed prognostic models was mainly attributed to the use of multiple preoperative ultrasound images from the same patient to generate statistical radiomic features, rather than simply using the largest tumor ROI among them. The models also revealed that the roundness of tumor lesion shape was positively correlated with prognosis for ovarian cancer. In summary, the newly developed prognostic models based on statistical radiomic features from ultrasound images were highly predictive of the risk of cancer-related death and possible recurrence not only for patients with epithelial ovarian cancer but also for those with nonepithelial ovarian cancer. They thereby provide reliable, non-invasive markers for individualized prognosis evaluation and clinical decision-making for patients with ovarian cancer.

Impact of neoadjuvant compared to adjuvant chemotherapy on prognosis in patients with hormone-receptor positive / HER2-negative breast cancer: A propensity score matching population-based study

BackgroundThe aim of this population-based cohort study was to investigate the impact of neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy in prognosis among patients with HR+/HER2 negative breast cancer. MethodThis population-based study utilized data from the research database BCBaSe 3.0, based on the Swedish National Quality breast cancer register, including all patients with breast cancer diagnosis in Sweden between 2008 and 2019. Propensity score matching approach was applied. The outcomes of interest consisted of distant-disease free (DDFS), breast-cancer specific (BCSS), and overall survival (OS). ResultsIn total, 14 459 patients were included in the study cohort of whom 2086 received NACT. After 1:1 propensity score matching (PSM), 1539 patients in each study group were available for analyses. No statistically significant difference in survival outcomes were observed between patients treated with NACT compared to those treated with adjuvant chemotherapy (Hazard Ratio (HR) for DDFS: 1.20; 95 % CI: 0.80–1.79; HR for BCSS: 1.16; 95 % CI: 0.54–2.49; HR for OS: 1.14; 95 % CI: 0.64–2.05). ConclusionIn this population-based cohort study of patients with HR+/HER2-breast cancer, the use of NACT seems to be comparable to adjuvant chemotherapy in terms of prognosis, although non-inferiority cannot be proven by this study design. Until further evidence suggesting a survival benefit in favor of either treatment is available, NACT can be pursued when surgical-de-escalation is intended.

CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study

BackgroundTumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes.MethodsWe investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women’s Circle of Health Study and Women’s Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43–12.33).ResultsWomen with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16–0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12–0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71–1.10).ConclusionsIn contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer.Trial registrationNot applicable.

Abstract PO1-03-03: STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival

Abstract Background: Standardized definitions of efficacy endpoints are needed to improve clinical trial designs, data reporting and interpretation of results, and to allow cross-trial comparisons. STEEP (Standardized Definitions for Efficacy Endpoints) criteria were proposed in 2007 by an expert panel from the National Cancer Institute (NCI) to provide common definitions for clinical trials in early breast cancer (BC). Invasive disease-free survival (IDFS) was selected as a candidate surrogate endpoint for overall survival (OS) in adjuvant trials and has been widely used in the last 15 years. Advances in BC systemic treatment led to review these criteria (STEEP v2.0), with the definition of a new modified endpoint: invasive BC-free survival (IBCFS). IBCFS excludes second primary non-breast invasive cancers from IDFS which may better detect efficacy effects when the toxicity profile of the intervention is well-known and the risk of second primary cancer is small. Methods: We proposed a multi-trial analysis of 8 adjuvant chemotherapy (CT) trials from GEICAM and TRIO to evaluate the different surrogate endpoints defined in the STEEP v2.0. Trial-level surrogacy was assessed through correlation between the ln hazard ratio (HR) of OS and the ln HR of the different studied endpoints across trials. The correlation was estimated by the weighted, by trial size, least squares regression (WLS) line and evaluated comparing the R2 values between OS and the corresponding endpoint tested. Primary analyses evaluated the correlation of OS with IDFS/IBCFS. Secondary analyses evaluated the correlation of OS with other STEEP v2.0 endpoints (distant disease-free survival [DDFS], distant relapse-free survival [DRFS], recurrence-free survival [RFS], recurrence-free interval [RFI] and distant recurrence-free interval [DRFI]) and explored the surrogacy between OS and all endpoints in specific groups of patients (pts) according to their risk of relapse: hormone receptors positive (HR+)/HER2-negative (HER2-) pts with intermediate/high and high-risk and triple negative (TN) pts. Results: A total of 14,473 pts were included. Median age was 50 years (range, 20–82). All were female, and 51.8% were postmenopausal. With a median follow-up of 115 months (range, 0.0–188) we found 2,504 OS events, 4,146 IDFS events (60.9% being distant recurrences) and 3,810 IBCFS events (62.4% being distant recurrences). For each trial, HR of OS, IDFS and IBCFS indicated same conclusions. If HR&amp;lt; 1 for OS, it was also for IDFS and IBCFS and the same was true when HR &amp;gt;1. R2 results of the weighted linear correlations between the ln HR of OS versus (vs) IDFS and OS vs IBCFS were 0.86 and 0.89, respectively. Confidence intervals (CI) at 95% were both overlapping. All other efficacy endpoints showed strong correlation with OS in the overall analysis. R2 values for HR+/HER2- intermediate/high and high-risk pts were 0.89 (OS vs IDFS) and 0.84 (OS vs IBCFS). For TN pts the correlations were weaker, being 0.63 (OS vs IDFS) and 0.73 (OS vs IBCFS). All WLS R2 values are described in the table. Conclusions: All tested STEEP v2.0 endpoints were strongly correlated with OS (R2 close to 1), meaning that their use as surrogate endpoints for adjuvant CT trials is appropriate. Notably, no differences were found between them in this multi-trial analysis. Therefore, none of them is more appropriate than other to discriminate the value of a new intervention vs comparator in adjuvant CT studies with mature data and long-term follow-up. Table: Citation Format: Sara López-Tarruella, Marina Pollan, Ander Urriticoechea, Eva Carrasco, Gonzalo Spera, Miguel Martín, Begoña Bermejo, Linnea Chap, Manuel Ruíz - Borrego, John Crown, Jose Angel García-Sáenz, Arlene Chan, Angel Guerrero, Valerie Bee, Lourdes Calvo, Rodrigo Fresco, Andrea Blasco, Andrés Hernando, Dennis Slamon. STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-03.

Abstract PO1-03-07: Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level

Abstract Background: Pathological complete response (pCR) has been used as a primary endpoint in neoadjuvant clinical trials for non-metastatic breast cancer and as a surrogate endpoint for long-term survival outcomes. The U.S. Food and Drug Administration (FDA) accepted pCR as a surrogate endpoint for the approval of new drugs in the neoadjuvant setting in high-risk early-stage breast cancer. However, though the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) pooled analysis in 2014 showed that at the patient level achieving pCR was associated with longer overall survival (OS) and event-free survival (EFS), at the trial-level the association between high pCR rate and better OS and EFS outcomes was weak (coefficient of difference [R2]; 0.03 and 0.24, respectively) among all subtypes of breast cancer. A recent study reported that this association at the trial-level was similarly weak among Human Epidermal Growth Factor Receptor-2 (HER-2) positive breast cancer (R2; 0.02 and 0.23, respectively). However, the potential surrogacy of pCR rate for OS and EFS in triple-negative breast cancer (TNBC) in the neoadjuvant setting has not been well studied in a comprehensive manner. Moreover, because of significant advances in systemic treatment strategies in TNBC over the past decade including a combination of immune checkpoint inhibitors (ICIs) with conventional cytotoxic agents, the trial-level surrogacy needs to be reassessed in recently published neoadjuvant clinical trials for TNBC. Our primary objective is to assess the association between pCR rate and survival outcomes in neoadjuvant clinical trials for TNBC by collecting data from articles published after the CTNeoBC article in 2014. Methods: We performed a systematic literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed, Cochrane Library, and Web of Science databases. Articles published between January 1, 2014, and March 31, 2023, were searched. We included only randomized control trials of neoadjuvant treatments for clinical stage I-III TNBC that compared two or more regimens followed by curative intent breast surgery. The selected trials had data for odds ratio (OR) for pCR and hazard ratios (HRs) either for OS or for EFS or disease-free survival (DFS). We excluded trials including estrogen receptor positive, progesterone receptor-positive, or HER-2 positive diseases, and those without data enough to obtain ORs for pCR, HRs for OS, EFS, or DFS. Unpublished data as a full article was also excluded. If EFS could not be obtained from the articles, DFS was used in place of EFS. Two independent investigators (TY and TF) searched and extracted data. Any disagreement was resolved by discussion with the third author (ZZ). A linear regression model on a logarithmic scale weighted by the sample size of each trial was performed and the R2 was used to assess the trial-level association between OR for pCR and HRs for OS or EFS. Results: We identified eight trials with a total of 2,926 patients. Three of the eight trials used ICIs in the intervention arm. One trial did not provide OS data and was not included in the OS analysis. In four trials, EFS was not available and DFS was used for EFS analysis. The R2 was 0.191 (95% confidence interval [CI], 0.165 to 0.218) for OS and 0.193 (95% CI, 0.167 to 0.219) for EFS. Conclusions: Similarly to the previous reports, our findings suggest that the surrogacy of the pCR rate for OS and EFS in recent neoadjuvant clinical trials for TNBC is weak. At this moment, there is no strong evidence to support using pCR as a surrogate for long-term survival outcomes in neoadjuvant clinical trials for TNBC. Citation Format: Toru Yoshino, Zao Zhang, Ryota Sato, Stanley Lipkowitz, Takeo Fujii. Revisiting the potential of pathological complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer at the trial-level [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-07.

Abstract PO4-05-10: A Carryover Effect: Antibody Drug Conjugates Constantly Provide a Substantial Improvement in Overall Survival more than in Progression-free Survival

Abstract Background: In metastatic breast cancer (MBC), progression-free survival (PFS) improvement does not always translate into overall survival (OS) benefit. Multiple treatment options after progression resulted in a long post-progression survival in MBC patients, and these would make the dissociation of PFS benefit and OS benefit. We have reported the constant correlation of PFS improvement and OS improvement in anti-HER2 containing treatment (Breast 2021; 59:211-220). The relationship between PFS and OS improvement in antibody drug conjugate has not been thoroughly examined. Methods: “Metastatic breast cancer” and “antibody drug conjugate” (ADC) were used as keywords to search for randomized clinical trials that report both PFS and OS. Hazard ratios (HR) and median survival were analyzed. Increments in PFS (delta PFS) and increments in OS (delta OS) were compared between studies. Results: A total of 8 trials were identified and summarized in table 1. The target of ADC was HER2 (N=6) or Trop2 (N=2). In DESTINY-Breast 03 trial, the control arm was another ADC (T-DM1). The control arms in all the other 7 trials were chemotherapy. The HR of PFS (range 0.28-0.66) was smaller than HR of OS (range 0.48- 0.83) in all of the trials. The median OS was not reached (NR) in 1 of the trials (DB-03) and was thus removed from the analysis for delta PFS and delta OS. In the comparison of delta PFS, the increments of median PFS fell between 1.5 and 10.9 months(m). The increments of median OS were between 1.6 and 12.7 m. All the delta OS are greater than the delta PFS in the 7 trials with available PFS and OS data. Conclusion: In MBC, ADCs targeting HER2 and Trop2 both constantly provide improvement of OS greater than PFS. Further investigation on the potential mechanism is warranted. Table 1 Citation Format: I-Chun Chen, Ching-Hung Lin, Yen-Shen Lu. A Carryover Effect: Antibody Drug Conjugates Constantly Provide a Substantial Improvement in Overall Survival more than in Progression-free Survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-10.

Abstract PO5-21-09: Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer

Abstract Background Sacituzumab govitecan (SG) is a Trop-2directed antibody-drug conjugate approved for second-line or later (2L+) treatment of metastatic triple-negative breast cancer in multiple countries and for 2L+ treatment of HR+/HER2‒ (IHC 0, 1+, or 2+/ISH) metastatic breast cancer (mBC) in the US. SG significantly improved progression-free survival (PFS) and overall survival (OS) vs treatment of physician’s choice (TPC) in patients (pts) with pretreated, endocrine-resistant HR+/HER2‒ mBC in the TROPiCS-02 study. The incidence of HR+/HER2‒ mBC increases with age, especially after 65, and older pts often have poorer prognosis due to comorbidities, increased toxicity, and reduced efficacy of chemotherapy. In TROPiCS-02, pts aged ≥ 65 years (yr) derived consistent PFS benefit and clinically meaningful improved OS with SG vs TPC. In this analysis, we present additional efficacy and safety outcomes by age subgroup. Methods Pts with HR+/HER2‒ mBC who had received at least 1 endocrine therapy, taxane, and CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy for mBC, were randomized to either SG (10 mg/kg IV days 1 and 8, Q3W) or TPC. The primary end point was PFS, and secondary end points included OS, objective response rate (ORR), and safety. A post hoc analysis was conducted by age subgroups (&amp;lt; 65 vs ≥ 65, &amp;lt; 75 vs ≥ 75). Results In total, 543 pts were randomized to the SG (n = 272; 73 [27%] ≥ 65, 16 [6%] ≥ 75) and TPC (n = 271; 67 [25%] ≥ 65, 8 [3%] ≥ 75) groups. Baseline characteristics were generally similar across treatment arms in each age subgroup, but a higher proportion of pts had performance status 1 vs 0 in the ≥ 65 vs &amp;lt; 65 and ≥ 75 vs &amp;lt; 75 subgroups, respectively. The data cutoff date was July 1, 2022. SG demonstrated longer median PFS and OS vs TPC across age subgroups. Hazard ratios (HR) for PFS with SG vs TPC were 0.69, 0.59, 0.70, and 0.30 for the &amp;lt; 65, ≥ 65, &amp;lt; 75, and ≥ 75 subgroups, respectively (Table). The HR for OS were 0.81, 0.80, 0.82, and 0.56 in these subgroups, respectively (Table). Median duration of response (DoR) was also longer with SG vs TPC across age subgroups, although median DoR was not estimable in the ≥ 75 subgroup (Table). ORR was higher with SG vs TPC, except in the ≥ 75 subgroup (Table). Safety was generally similar with SG vs TPC across subgroups with the following differences. Grade ≥ 3 treatment-emergent adverse events were more common in the ≥ 75 subgroup than the other subgroups (SG, 81% in ≥ 75 vs 68%-73% for all others; TPC, 71% in ≥ 75 vs 60%-61% for all others). TEAEs leading to dose reduction were also more common in pts treated with SG in the ≥ 75 subgroup, but were consistent across other subgroups (Table). However, sample sizes in the ≥ 75 subgroup were small, which limits interpretation (Table). TEAEs leading to treatment discontinuation were more common in older pts, irrespective of treatment group (Table). Conclusions SG showed benefit in PFS and OS vs TPC in pts with HR+/HER2‒ mBC across age subgroups, consistent with the intent to treat population. SG was associated with a slight increase in toxicity for elderly pts, as expected. SG demonstrated a favorable benefit/risk profile, with efficacy benefit and acceptable toxicity, for elderly pts. Table. Citation Format: Aditya Bardia, Peter Schmid, Sara Tolaney, Frederik Marmé, Javier Cortés, Theresa Valdez, Hao Wang, Wendy Verret, Hope Rugo. Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2‒ metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-09.

Abstract PO3-01-04: Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study

Abstract Introduction Neoadjuvant therapy (NAT) is considered the standard of care in patients with HER2-positive breast cancer mainly due to the possibility to adjust the post-neoadjuvant treatment based on the tumor response to NAT. However, there is no convincing evidence on a survival benefit with NAT compared to adjuvant therapy (AT) for HER2-positive breast cancer. The aim of the present study was to compare the two therapeutic strategies in a register-based cohort of Swedish patients with primary operable HER2-positive breast cancer. Method The research database BCBaSe 3.0, which is based on the Swedish National Quality breast cancer register, was used to identify patients with primary operable HER2-positive breast cancer that diagnosed between 2008 and 2020 and received either NAT or AT including chemotherapy and trastuzumab. To mitigate confounding by indication bias, propensity score matching (PSM) with 1:1 matching was applied. The effectiveness of the two therapeutic strategies was investigated through analyzing distant disease-free survival (DDFS), breast-cancer specific survival (BCSS), and overall survival (OS). Multivariate Cox regression analyses were performed for the outcomes of interest to provide Hazard Ratios (HR) and corresponding 95% Confidence Intervals (CI). Results In total, 7258 patients with primary operable HER2-positive breast cancer treated with either NAT or AT were identified, 1789 (24.6%) received NAT and 5469 (75.4%) AT. After 1:1 PSM, 1258 patients in each therapeutic strategy were available for comparisons. After a median follow-up of 63 months, no statistically significant differences between NAT and AT were observed in either outcome (HR for DDFS: 0.97; 95% CI: 0.72 – 1.30; HR for BCSS: 0.69; 95% CI: 0.45 – 1.07; HR for OS: 0.72; 95% CI: 0.50 – 1.05). In subgroup analyses, estrogen-receptor status did not impact the results that remained statistically non-significant between NAT and AT whereas in patients with clinically positive lymph node status, NAT resulted in better BCSS (HR: 0.44; 95% CI: 0.22 – 0.89) and OS (HR: 0.49; 95% CI: 0.29 – 0.90). The latter trend was not evident in patients with clinically negative lymph node status. Conclusion Our study results confirm the equivalence of NAT and AT in terms of prognosis for patients with operable HER2-positive disease and imply a potential benefit of NAT compared to AT in patients with clinically positive lymph node status. Considering the emerging treatment strategies in HER2-positive breast cancer patients treated with NAT (pertuzumab as a part of NAT, T-DM1 as post-neoadjuvant therapy) that have been shown to improve survival but are not reflected in the study cohort, NAT should be considered as the strategy with the higher possibility to improve long-term prognosis for patients with HER2-positive disease. Citation Format: Servah Hosseini-Mellner, Åsa Wickberg, Antonis Valachis, Andreas Karakatsanis. Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-04.

Abstract PO5-25-10: Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways Study

Abstract Background: A subset of breast cancers (BC) typically classified as HER2-negative do express low levels of the protein and can be responsive to targeted therapy trastuzumab-deruxtecan. It is unclear if HER2-low tumors have a biology distinct from that in HER2 negative BC. The goal of this study was to evaluate the clinical and epidemiologic features of tumors with HER2-low expression compared with those classified as HER2-negative in a large population study. Material and methods: The Pathways Study is a prospective multi-ethnic cohort study of women with BC enrolled between 2006-2013 within Kaiser Permanente Northern California (KPNC). Breast biomarker results were extracted from pathology reports and underwent centralized pathology review. HER2-low was defined as 1+ or 2+ (negative by in situ hybridization); HER2-negative was defined as 0+. Other data were collected by self-report or extraction from electronic health records at the KPNC cancer registry, including BC risk factors, tumor characteristics [AJCC stage, ER/PR positive or negative status], treatment modality (chemotherapy, radiation therapy, hormonal therapy, and type of surgery), and survival outcomes [recurrence free survival (RFS), breast cancer specific mortality (BCSM), and overall survival (OS)]. The clinical and epidemiologic variables were tested in association with HER2 status (low/negative) by t-tests. Associations of HER2-low with survival outcomes were calculated by proportional hazards regression. Women were included in this analysis if they had a documented HER2 value that was not classified as HER2-positive. Results: Of the 2,200 eligible cases, 1,295 (57.2%) had tumors that were HER2-low. Hormone receptors (HR) were positive in 1,956 (88.9%) cases. HER2-low expression was observed more often in HR-positive cases than in HR-negative, 1,144 (58.4%) vs. 115 (47.1%), respectively (p=.0005). Patients with HER2-low tumors were less likely than those with HER2-negative BC to have family history: 232 of 1259 (18.6%) vs. 214 of 941 (22.8%), respectively (p=.015). This difference was true for patients with HR-positive tumors but not for HR-negative. HER2-low expression appeared to be more common in Asian patients in the HR-negative group than in patients from any other race or ethnicity group. In the HR-negative group, patients with HER2-low had better OS, BCSM, and RFS (p=.019, .014, and .034, respectively) than those with HER2-negative disease. Multivariable analyses were performed for the HR-negative group and adjusted for age at diagnosis, tumor AJCC stage, and type of treatment. Compared with patients with HER2-negative status, patients with HER2-low tumors had lower risk for OS (hazard ratio=0.48, 95% confidence interval: 0.28 to 0.81, p= .006); for RFS (hazard ratio=0.49, 95% confidence interval: 0.27 to 0.90, p= .021); and for BCSM (hazard ratio=0.36, 95% confidence interval: 0.17 to 0.76, p= .007). In analyses stratified by race and ethnicity and controlled for age at diagnosis, AJCC stage and treatment type, Black patients with HER2-low tumors had lower risk for RFS (hazard ratio=0.44, 95% confidence interval: 0.21 to 0.94, p= .035) compared with patients with HER2-negative tumors. Conclusions: In this large prospective study with well annotated epidemiologic, clinical, and outcome data, we observed some clinical and epidemiologic differences between HER2-low and HER2-negative patients, raising the possibility that HER2-low might be a unique biologic entity. Citation Format: Thaer Khoury, Rochelle Payne Ondracek, Song Yao, Lucas Mendocino, Warren Davis, Angela Omilian, Marilyn Kwan, Janise Roh, Lia D'Addario, Emily Valice, Daniel Fernandez, Isaac Ergas, Christine Ambrosone, Lawrence Kushi. Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-10.

Abstract RF01-03: PARSIFAL-LONG: Extended follow-up of hormone receptor-positive/HER2-negative advanced breast cancer patients treated with fulvestrant and palbociclib vs. letrozole and palbociclib in the PARSIFAL study

Abstract Background: The Phase 2 PARSIFAL study assessed whether fulvestrant (FUL) or letrozole (LET) was the optimal endocrine partner for the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib (PAL) in patients (pts) with untreated, endocrine-sensitive, hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer (ABC) in the first-line setting. This trial failed to demonstrate an improvement in progression-free survival (PFS) of PAL+FUL over PAL+LET (Llombart-Cussac et al. Jama Oncol 2021). Following progression on CDK4/6i-based regimens in the metastatic setting, the EMERALD study (Bardia et al, SABCS 2022 GS3-01) identified early progressions (&amp;lt; 12 months [mo]) as a strong predictor of resistance to subsequent endocrine therapies. Here, we report updated PFS and overall survival (OS) from PARSIFAL, exploring a PFS &amp;lt;12 mo threshold as a prognostic factor for poor outcomes. Methods: This was an observational, international, multicenter study that included pts from the prospective PARSIFAL study, in which pts were randomly assigned (1:1) to receive PAL (oral 125 mg/day, 28-day cycles; 3 weeks on, 1 week off) plus FUL or LET at conventional doses. The primary objective was to extend the assessment of OS of PARSIFAL study with a longer median follow-up. Secondary objectives included extended PFS, other post-progression efficacy data, and the identification of new prognostic and predictive markers. The design had a planned recruitment of at least 388 pts with 195 deaths. The 2-sided stratified log-rank test (α = 0.05) had a 70% power to detect a hazard ratio ≤0.70 in favor of FUL + PAL arm. Results: A total of 389 pts (80.5%) from the PARSIFAL study were included in this analysis, involving 32 of the 47 original sites. Pts signed a new informed consent form according to local regulations. Demographic and baseline disease characteristics were similar between the PARSIFAL-LONG and the overall PARISFAL intention-to-treat populations. At the time of analysis, after a median follow up of 5.0 years (range, 0.1-7.3), 241 and 213 events were reported for PFS and OS, respectively. No differences in efficacy were observed between treatment arms whether for PFS (hazard ratio, 1.0, p=0.985) or OS (hazard ratio, 0.94, p=0.635). In accordance with the protocol for PARSIFAL-LONG, both arms were combined for subsequent analysis. The median PFS (mPFS) for the first-line PAL-based regimen population was 33.2 mo (95%CI, 27.7-39.5), with a median OS (mOS) of 65.4 mo (95%CI, 57.8-72.0). A total of 86 pts (22.1% of the population) had a mPFS time &amp;lt;12 mo (early progressors). mOS and mPFS for this early progressor subgroup were 24.0 mo (95%CI, 17.3-30.1) and 7.0 mo (95%CI, 5.6-8.3), respectively, and only 11 pts (12.8%) were still alive at the time of analysis. The remaining 303 pts (77.9%) were progression-free on PAL-based regimens at 12 mo (PFS≥12). The number of events for PFS and OS at this time were 165 (54.5%) and 138 (45.5%), respectively. mOS from randomization for the PFS≥12 subgroup was 81.5 mo (95%CI, 70.2-not achieved) and the mPFS was 49.8 mo (95%CI, 40.9-59.8). Following progression on PAL-based regimens, the PFS≥12 criteria was a strong predictor for mOS, with 27.0 vs 18.0 mo (hazard ratio, 0.67, 95%CI, 0.51-0.90, p=0.007) for PFS≥12 and early progressors, respectively. These differences may increase in the future, as 54.5% of pts with PFS≥12 are still alive compared to 12.8% of pts with an early progression. Conclusions: Extended follow-up analysis from PARSIFAL study confirms no major differences between LET or FUL when combined with PAL. mPFS and mOS results are consistent with those reported in other first-line trials involving different CDK4/6i. Progression within the first year of first-line CDK4/6i-based regimen for HR+/HER2- ABC pts may be prognostic of less favorable outcomes. Citation Format: Antonio Llombart-Cussac, José Manuel Pérez-García, Meritxell Bellet- Ezquerra, Florence Dalenc, Miguel Gil-Gil, Manuel Ruíz - Borrego, Joaquín Gavilá, Peter Schmid, Pilar Zamora, Duncan Wheatley, Eduardo Martínez-de Dueñas, Kepa Amillano, Antonio Antón, Paul Cottu, Gemma Viñas, Thierry Petit, Petra Tesarová, Juan Cueva, Marco Colleoni, Maria Purificación Martínez del Prado, Raquel Andrés, Marta Díaz Cabo, Susana Victorino, Miguel Sampayo-Cordero, Javier Cortés. PARSIFAL-LONG: Extended follow-up of hormone receptor-positive/HER2-negative advanced breast cancer patients treated with fulvestrant and palbociclib vs. letrozole and palbociclib in the PARSIFAL study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF01-03.

Abstract PO1-28-09: Rethinking the value of pathologic complete response rate for the survival outcomes of early triple-negative breast cancer treated with neoadjuvant chemotherapy: a systematic review and network meta-analysis

Abstract Background: Neoadjuvant chemotherapy (NACT) has been more frequently used in breast cancer, but it’s controversial whether NACT or adjuvant chemotherapy (ACT) is more effective in improving survival outcomes for triple-negative breast cancer (TNBC) patients. Recent studies also proposed pathologic complete response (pCR) could not be a robust surrogate for survival outcomes in certain types of breast cancer. To address these questions, a general meta-analysis and a network meta-analysis (NMA) were conducted to compare the survival outcomes of patients with pCR, non-pCR after NACT and ACT. The cut-off pCR rate was also declared to indicate when NACT produces equivalent survival outcomes to ACT (Registration: PROSPERO CRD42022336732). Methods: Databases including PubMed, Embase, Web of science and Cochrane library were searched up to June 2023 to investigate studies comparing NACT and ACT, as well as randomized controlled trials (RCTs) comparing different regimens in NACT or ACT settings in early operable TNBC patients. Heterogeneity was assessed using χ² based Q-test and I², combined with hazard ratios (HRs) with 95% confidence intervals (CI) computed for overall survival (OS), and disease-free survival (DFS, or event-free survival). The NMA with a Bayesian framework was conducted using both random and fixed effect model. The Weighted Least Square method and the Least Absolutely Deviation method were used to determine the cut-off pCR rates of OS and DFS. Results: A total of 35 studies involving 21 RCTs and 34143 TNBC patients were included. The general meta-analysis comprised 14 cohort studies. Eight high-quality cohort studies with propensity score matching and 21 RCTs were included in NMA. The pooled pCR rate for NACT was 42.2% (95% CI 37.8%-46.8%). Overall, the NACT cohort showed significantly worse OS and DFS than ACT cohort (HR=1.67, 95% CI 1.22-2.31; HR=1.37, 95% CI 1.14-1.64). However, patients with pCR after NACT showed improved OS than ACT (HR=0.58, 95% CI 0.50-0.66), while the patients without pCR after NACT had pooper OS than ACT (HR=2.03, 95% CI 1.88-2.19). As for DFS, there was no statistically difference between pCR after NACT and ACT groups (HR=1.04, 95% CI 0.63-1.73), while patients without pCR after NACT had significantly worse DFS than ACT (HR=2.65, 95% CI 1.98-3.55). From the NMA, the OS and DFS were better when combining modern target therapy such as Bevacizumab, PARPi, and PD-1/PD-L1 inhibitor (Figure 1), but not achieving pCR completely negated the benefits of newer drugs. Adding adjuvant capecitabine to patients not achieving pCR seemed to favor the OS. It was predicted that when the pCR rates were 64.7% and 46.9% (Figure 2), respectively, the OS and DFS of patients treated with NACT would be the same as those of patients treated with ACT. Conclusions: Higher pCR rate after NACT was associated with improved OS compared with ACT in TNBC patients. However, failure to achieve pCR after NACT resulted in worse survival outcomes than ACT. NACT had similar survival outcomes with ACT only when the pCR rate was at least 46.9%. The development of effective NACT regimens is beneficial for breast cancer patients. Figure 1. Forest plot of the Hazard Ratio for OS and DFS in TNBC patients pCR: pathological complete response; Bev: Bevacizumab; Pt: platinum; NACT: neoadjuvant chemotherapy; ACT: adjuvant chemotherapy; vel: veliparib; PDi:PD1/PDL1 inhibitor; X: capecitabine Figure 2. The cut-off value of pCR when NACT and ACT have the same Hazard Ratio based on OS and DFS. pCR: pathological complete response; Bev: Bevacizumab; Pt: platinum; NACT: neoadjuvant chemotherapy; ACT: adjuvant chemotherapy Citation Format: Xiaoying Qiao, Shu Wang, Taobo Hu, Baosheng Liang. Rethinking the value of pathologic complete response rate for the survival outcomes of early triple-negative breast cancer treated with neoadjuvant chemotherapy: a systematic review and network meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-09.

Pathologic and survival outcomes following radical cystectomy for “progressive” and “de novo” muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status

ObjectiveTo compare survival and pathologic outcomes in patients with progressive muscle-invasive bladder cancer (pgMIBC) and de novo muscle-invasive bladder cancer (dnMIBC) after radical cystectomy (RC), with a focus on the role of neoadjuvant chemotherapy (NAC). MethodsA comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), and pathologic outcomes (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. ResultsThe analysis included 19 cohorts from 16 studies, categorized into 3 groups based on NAC use: 1. patients who underwent RC and were all treated with NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05–2.2), while the HR for OS was 1.46 (95%CI = 1.05–2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05–1.55), and the HR for OS was 1.27 (95%CI = 1.08–1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12–1.84). ConclusionsThe findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC.

IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.

Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P= 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.

Treatment strategies for stage IA non-small cell lung cancer: A SEER-based population study.

There are various therapeutic methods for treating stage IA (T1N0M0) non-small cell lung cancer (NSCLC), but no studies have systematically assessed multiple treatments to determine the most effective therapy. Stage IA NSCLC patient data collected between 2004 and 2018 were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Treatment modalities included observation, chemotherapy alone (CA), radiation alone (RA), radiation+chemotherapy (RC), surgery alone (SA), surgery+chemotherapy (SC), surgery+radiation (SR) and surgery+radiation+chemotherapy (SRC). Comparisons were made of overall survival (OS) and lung cancer-specific survival (LCSS) among patients based on different therapeutic methods by survival analysis. Ultimately, 89147 patients with stage IA NSCLC between 2004 and 2018 were enrolled in this study. The order of multiple treatment modalities based on the hazard ratio (HR) for OS for the entire cohort revealed the following results: SA (HR: 0.20), SC (HR: 0.25), SR (HR: 0.42), SRC (HR: 0.46), RA (HR: 0.56), RC (HR: 0.72), CA (HR: 0.91) (P<0.001), and observation (HR: Ref). The SA group had the best OS and LCSS, and similar results were found in most subgroup analyses (all P<0.001). The order of surgical modalities based on the HR for OS for the entire cohort revealed the following results: lobectomy (HR: 0.32), segmentectomy (HR: 0.41), wedge resection (HR: 0.52) and local tumor destruction (HR: Ref). Lobectomy had the best effects on OS and LCSS, and similar results were found in all subgroup analyses (all P<0.001). SA appeared to be the optimal treatment modality for patients with stage IA NSCLC, and lobectomy was associated with the best prognosis. There may be some indication and selection bias in our study, and the results of this study should be confirmed in a prospective study.

Pharmacogenomic study of gemcitabine efficacy in patients with metastatic pancreatic cancer: A multicenter, prospective, observational cohort study (GENESECT study).

Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy. This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%. In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p=.007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p=.019). Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS.

Simultaneous boost radiotherapy versus conventional dose radiotherapy for patients with newly diagnosed glioblastoma: a multi-institutional analysis

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan–Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27–0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

Breakthrough Therapy Cancer Drugs and Indications With FDA Approval: Development Time, Innovation, Trials, Clinical Benefit, Epidemiology, and Price.

The breakthrough therapy designation (BTD) facilitates the development of drugs with a large preliminary benefit in treating serious or life-threatening diseases. This study analyzes the FDA approval, trials, benefits, unmet needs, and pricing of breakthrough and nonbreakthrough therapy cancer drugs and indications. We analyzed 355 cancer indications with FDA approval (2012-2022). Breakthrough and nonbreakthrough indications were compared regarding their FDA approval, innovativeness, clinical trials, epidemiology, and price. Data were extracted from FDA labels, the Global Burden of Disease study, and the Centers for Medicare & Medicaid Services. Hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS), and relative risk (RR) of tumor response were meta-analyzed across randomized controlled trials. Objective response rates (ORRs) were meta-analyzed for single-arm trials. We identified 137 breakthrough and 218 nonbreakthrough cancer indications. The median clinical development time was 3.2 years shorter for breakthrough drugs than for nonbreakthrough drugs (5.6 vs 8.8 years; P=.002). The BTD was more frequently granted to biomarker-directed indications (46% vs 34%; P=.025) supported by smaller trials (median, 149 vs 326 patients; P<.001) of single-arm (53% vs 27%; P<.001) and phase I or II design (61% vs 31%; P<.001). Breakthrough indications offered a greater OS (HR, 0.69 vs 0.74; P=.031) and tumor response (RR, 1.48 vs 1.32; P=.006; ORR, 52% vs 40%; P=.004), but not a PFS benefit (HR, 0.53 vs 0.58; P=.212). Median improvements in OS (4.8 vs 3.2 months; P=.002) and PFS (5.4 vs 3.3 months; P=.005) but not duration of response (8.7 vs 4.7 months; P=.245) were higher for breakthrough than for nonbreakthrough indications. The BTD was more frequently granted to first-in-class drugs (42% vs 28%; P=.001) and first-in-indication treatments (43% vs 29%; P<.001). There were no differences in treatment and epidemiologic characteristics between breakthrough and nonbreakthrough drugs. Breakthrough drugs were more expensive than nonbreakthrough drugs (mean monthly price, $38,971 vs $22,591; P=.0592). The BTD expedites patient access to effective and innovative, but also expensive, new cancer drugs and indications.

Prognostic value of combined psoas muscle mass and controlling nutritional status in patients with pancreatic ductal adenocarcinoma: a retrospective cohort study.

Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.

Oncological Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide with versus without Confirmatory Bone Scan.

In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.