Objective: This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). Methods: Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing-remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received C 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. Results: This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of C 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCRtreated patients received treatment for C 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5-7.7) vs. oral DMT, 5.6 (2.6-12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval)-10.0% (-6.1 to-15.0%) vs. oral DMT,-13.0% (-8.5 to-17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval)-11% (-7.1 to-16.0%) vs. oral DMT,-9.7% (-5.0 to-14.0%) vs. injectable DMT]. Conclusion: This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.

BACKGROUND: Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been reported in the literature, the strength of evidence supporting each association can vary significantly. Even among the subgroup of drugs classified by the PharmGKB database to have a high or moderate level of evidence, there is limited information regarding the economic value of pharmacogenetic testing.OBJECTIVES: To: (a) summarize the available pharmacoeconomic evidence assessing the value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations; (b) determine the quality of the studies that contain this evidence; and (c) discuss the quality of this evidence with respect to the level of evidence of the drug-gene associations. METHODS:The PharmGKB database was used to identify cancer drugs with clinically relevant drug-gene associations graded high (1A, 1B) or moderate (2A, 2B). A systematic literature review was conducted using these drugs. Ovid MEDLINE and Embase databases were searched to identify costeffectiveness, cost-utility, or cost-minimization studies comparing pharmacogenetic testing to an alternative. Cost and effect values from every relevant comparison within the studies were extracted, and the incremental cost-effectiveness ratio (ICER) was either extracted or calculated for each comparison. Quality assessment was conducted for each study using the Quality of Health Economic Studies (QHES) instrument. Qualitative synthesis was used to summarize the data.

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1051 Background: Tucatinib (TUC) is an oral HER2-targeted therapy approved by the FDA in Apr 2020 for use in combination with trastuzumab and capecitabine (TRA+CAP) for patients with previously treated HER2+ metastatic breast cancer (MBC). In the randomized HER2CLIMB trial, median (95% CI) overall survival (mOS) and progression-free survival (PFS) for patients receiving TUC with TRA+CAP were 21.9 (18.3, 31.0) and 7.8 (7.5, 9.6) months, respectively. Median duration of therapy was 7.3 months. HER2CLIMB used a standard of care comparator arm and included patients with active and stable brain metastasis (BM). HER2CLIMB was conducted prior to approval of fam-trastuzumab deruxtecan (T-DXd) so did not assess the impact of TUC-based therapy following T-DXd. Objective: Describe patient characteristics, treatment patterns, and clinical outcomes for TUC-based treatment in the real-world setting. Methods: This retrospective study included patients in the Komodo Health dataset (aggregating data from patient administrative health claims in the United States) diagnosed with MBC between Jan 1, 2017 and Sep 3, 2022 and initiating TUC post- approval in Apr 2020. Patient characteristics were described in the baseline period (≤6 months from TUC initiation). Key outcomes were time to next treatment (TTNT; as a proxy for PFS), time to discontinuation (TTD), and persistence (proportion continuing treatment at each timepoint) in all TUC-treated patients, and in patients receiving TUC immediately following T-DXd. Results: Of 16,990 patients identified with HER2+ MBC, 528 received TUC-based treatment. Of these, 57 (11%), 164 (31%), 154 (29%), and 153 (29%) received TUC in first-line (1L), second-line (2L), third-line (3L), and fourth-line or later (4L+), respectively. Median follow-up from TUC initiation was 9 months. Overall, 400 patients (76%) had BM prior to initiating TUC (43 [75%], 138 [84%], 111 [72%], and 108 [71%] in 1L, 2L, 3L, and 4L+, respectively). Median (95% CI) TTNT was 10.7 (9.4, 13.1) months overall and 11.5 (9.6, 14.4) in patients receiving TUC in 2L or 3L. Median (95% CI) TTD was 8.5 (7.2, 9.3) months overall, and 9.1 (7.7, 9.9) in patients receiving TUC in 2L or 3L. TUC persistence in the overall cohort was 46% (91/200) at 12 months and 35% (40/115) at 18 months. Sixty-one patients (12%) received TUC immediately following T-DXd (median 4L; 12 in 2L/3L, 49 in 4L+); of whom 36 (59%) had BM prior to initiating TUC. TTNT and TTD for patients treated with TUC following T-DXd were 7.5 (5, 13.3) and 7.3 (3.2, 9.5) months, respectively. Conclusions: In the real-world setting, a higher proportion of patients receiving TUC had BM compared with the HER2CLIMB patient population. TUC-based treatment in the real world is used in multiple lines of therapy and is associated with a similar TTNT and TTD to PFS observed in HER2CLIMB, inclusive of a cohort of patients who received TUC following T-DXd therapy.