Pfizer (Sweden)

Abstract Background: While progression-free survival (PFS) often serves as a surrogate endpoint in metastatic breast cancer (mBC) treatment approvals, it is unclear whether patients prefer PFS to overall survival (OS), or whether patients are willing to accept greater uncertainty in OS in exchange for more immediate PFS gains. Methods: A nationwide survey was administered to US women aged ≥ 21 years. The survey asked respondents to imagine they were a mBC patient choosing between two hypothetical mBC treatment options (Table): a “certain OS” option (PFS=5.5 months, OS=24 months) versus an “uncertain OS” option defined as having higher PFS (8 months) and uncertain OS with the possibility of both higher OS (80% chance of OS=28 months) as well as lower OS (20% chance of OS=22 months). A multiple random staircase design was used to iteratively adjust OS probabilities in the “uncertain OS” option until the respondent was indifferent between the “certain OS” treatment option with 5.5-month PFS and the “uncertain OS” treatment option with 8-month PFS. The point of indifference was estimated by taking the midpoint between the maximum and minimum expected OS values for the "uncertain OS" treatment option, as observed in the final question of the multiple random staircase. The value of the increase in PFS was the difference between the expected OS of the “uncertain OS” option at the indifference point and the risk-neutral expected OS (26.8 months). Results: The 306 respondents had an average age of 52 years, 94% were insured, 76% were white, and 52% had a bachelor’s degree or higher. Among these respondents, 53% preferred the “uncertain OS” option with greater PFS over the “certain OS” option with lower PFS at baseline. However, preferences were highly heterogeneous; 19.6% preferred the “uncertain OS” treatment even when the probability of lower OS (22 months) was 90% whereas 24.8% did not choose to take any risk and always preferred the “certain OS” option, even if the probability of greater OS (28 months) was 95%. On average, respondents valued the “uncertain OS” treatment profile more as they were willing to forego 0.96 months of certain OS in exchange for a 2.5-month increase in PFS and the possibility for extended survival. Conclusion: On average, women attributed more value to increases in PFS even if this meant there was some possibility of a lower OS. However, preferences varied significantly across individuals in the sample. Because, on average, patients are willing to trade off OS for increases in PFS, shared decision-making processes should be considered to ensure mBC patient care aligns with individual preferences. Citation Format: J. Kim, K. Spurrier, M. Jakobsson, B. Hauber, J. Doan, B. Korytowsky, J. Shafrin. Quantifying the value of progression-free survival in breast cancer treatment among a general population of US women [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-12-02.

Background:Tofacitinib is a Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Prospective real-world data are scarce.Objectives:To collect data on clinical outcomes, including health-related quality of life (HRQoL) and fatigue during treatment with tofacitinib.Design:This is a prospective observational multicentre study in Sweden. In this analysis, outcomes at weeks 2, 8 and 16 are reported.Methods:Patients with active UC confirmed with endoscopy or faecal calprotectin (FC) were enrolled during 2020–2023 when starting tofacitinib therapy.Results:In total, 103 patients were included. After 2 weeks of treatment, 50% (39/78) had achieved symptomatic response and at week 16, 39% (35/89) had achieved corticosteroid-free clinical remission according to the partial Mayo score. At week 16, a reduction in FC by ⩾50% was seen in 49% (35/71) and 24% (11/46) were in endoscopic remission. The frequency of arthralgia decreased from 29% (30/103) at baseline to 11% (10/89) at week 16. Regarding HRQoL at week 16; each of the four Short Health Scale dimensions (symptoms, social function, disease-related worry and general well-being) had improved by a median of 1 point (p < 0.01) and the European Quality of Life 5 Dimensions 5 Levels index improved from 0.80 to 0.87. Finally, the Inflammatory Bowel Disease Fatigue score measuring occurrence and severity showed an improvement with a decrease from 9 points at baseline to 6 at week 16 (p < 0.05).Conclusion:Induction therapy with tofacitinib therapy was associated with improvements in patient-reported outcome measures of symptoms, endoscopic activity, arthralgia, HRQoL and fatigue. These real-world data illustrate that tofacitinib is a fast-acting drug with broad therapeutic effects in UC.ClinicalTrial registration number:NCT04338204.

To evaluate economic outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) treated with a first- or second-line cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). This retrospective analysis utilized Optum's Clinformatics DataMart (January 1, 2014-September 30, 2021). Included patients had ≥1 pharmacy claim for palbociclib, abemaciclib, or ribociclib in first or second-line and ≥6 months of continuous health plan enrollment in preindex (index: date of first CDK4/6i claim) and follow-up periods. Mean all-cause per patient per month (PPPM) medical, healthcare resource utilization (HCRU) and costs, and outpatient pharmacy prescriptions costs were compared among CDK4/6is using stabilized inverse probability of treatment weighting (sIPTW). We identified 3,182 patients taking palbociclib, 286 taking abemaciclib, and 149 taking ribociclib, with median follow-ups of 20.8, 16.6, and 19.9 months, respectively. After sIPTW, palbociclib was associated with a lower risk of inpatient (IP) admissions versus abemaciclib (35.8% vs 41.6%; odds ratio: 1.31; P=0.034). No other significant differences were seen for HCRU. PPPM outpatient costs were significantly lower with palbociclib versus abemaciclib ($754; P=0.05). PPPM IP ($2,252 vs $6,286), medical ($6,948 vs $11,717), and total ($19,370 vs $23,639) costs were also lower with palbociclib versus abemaciclib, although not significant. There were no significant differences in PPPM HCRU or costs between palbociclib and ribociclib. In patients with Medicare, PPPM total medical costs were lower with palbociclib versus abemaciclib by $1,608 (P=0.04), while other costs were not significantly different. No significant differences in costs were seen with palbociclib versus ribociclib. All-cause HCRU and costs were generally not different between the CDK4/6is but favored palbociclib for medical (including IP) costs versus abemaciclib. Due to limited patient numbers, uncertainty exists about abemaciclib and ribociclib cost estimations. Further studies of HCRU and costs are needed to support a cost-minimizing strategy for mBC.

PurposeCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have improved patient survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC) in clinical trials and real-world studies. However, investigations of survival gains in broader HR+/HER2− mBC populations using epidemiological approaches are limited.MethodsThis retrospective study used SEER registry data to assess breast cancer-specific survival (BCSS) in patients diagnosed with HR+/HER2− de novo mBC from 2010 to 2019. Kaplan–Meier and Cox proportional hazards models were used to compare BCSS in patients diagnosed before (2010‒2013 with follow-up to 2014) and after (2015‒2018 with follow-up to 2019) the 2015 guideline recommendations for CDK4/6i use. A comparison was made to patients with HR+/HER2-positive (HER2+) de novo mBC, for which no major guideline changes occurred during 2015–2018.ResultsData from 11,467 women with HR+/HER2− mBC and 3260 women with HR+/HER2+ mBC were included. After baseline characteristic adjustment, patients with HR+/HER2− mBC diagnosed post-2015 (n = 6163), had an approximately 10% reduction in risk of BC-specific death compared with patients diagnosed pre-2015 (n = 5304; HR = 0.895, p < 0.0001). Conversely, no significant change was observed in HR+/HER2+ BCSS post-2015 (n = 1798) versus pre-2015 (n = 1462). Similar results were found in patients aged ≥ 65 years.ConclusionUsing one of the largest US population-based longitudinal cancer databases, significant improvements in BCSS were noted in patients with HR+/HER2− mBC post-2015 versus pre-2015, potentially due to the introduction of CDK4/6i post-2015. No significant improvement in BCSS was observed in patients with HR+/HER2+ mBC post-2015 versus pre-2015, likely due to the availability of HER2-directed therapies in both time periods.

1111 Background: Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts. Our primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset. Methods: We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included. Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses. Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively. Results: Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91). Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table). Conclusions: This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population. [Table: see text]

&lt;p dir="ltr"&gt;&lt;u&gt;Objective&lt;/u&gt;: Type 2 diabetes (T2D) increases the risk for major adverse liver outcomes (MALO), including cirrhosis and its complications. Patients with T2D frequently have other traits of the metabolic syndrome (MetS). It remains uncertain whether there is synergistic effect of accumulating MetS traits on future MALO risk.&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;u&gt;Research Design and Methods&lt;/u&gt;: Patients with T2D without a history of liver disease were identified from national registers in Sweden from 1998 to 2021. MetS traits included hypertension, low HDL level, hypertriglyceridemia, obesity, and albuminuria, in addition to T2D. MALO events were identified based on administrative coding from national registers until Oct 31, 2022. Data were analyzed using Cox regression models.&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;u&gt;Results&lt;/u&gt;: In total 230,992 patients were identified (median age: 64; 58% male), of which 3,215 (1.39%) developed MALO over a median follow-up of 9.9 years. Compared to patients with one MetS trait (only T2D) at baseline, those with more than one MetS trait had a higher rate of MALO (aHR=2.33, 95% CI=1.53-3.54). The rate of MALO increased progressively with increasing numbers of MetS traits at baseline (aHR=1.28 per added trait, 95% CI=1.23-1.33). During follow-up, patients that acquired additional MetS traits had progressively higher rate of MALO. The MetS trait with the largest association with incident MALO was hypertension (aHR=2.06, 95% CI=1.57-2.71).&lt;/p&gt;&lt;p dir="ltr"&gt;&lt;u&gt;Conclusion&lt;/u&gt;: Having or acquiring additional traits of the metabolic syndrome increase the rate of progression to major adverse liver outcomes in patients with type 2 diabetes. These results could be used to inform screening initiatives for liver disease.&lt;/p&gt;

Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.