Median To Treatment Discontinuation Research Articles

The journey of patients affected by metastatic hormone receptor-positive/HER2-negative breast cancer from CDK 4/6 inhibitors to second-line treatment: A real-world analysis of 701 patients enrolled in the GIM14/BIOMETA study

PurposeThe aim of this study was to evaluate the effectiveness of CDK 4/6 inhibitors (CDK 4–6i) according to HER2 status (low/zero), and endocrine resistance/sensitivity, as well as the efficacy of second-line treatments, in a large real-world cohort. MethodsThe GIM14/BIOMETA study (NCT02284581) is a retrospective/prospective study of the Gruppo Italiano Mammella evaluating treatment patterns and survival outcomes in patients with metastatic breast cancer (MBC). We retrieved data on patients with hormone receptor-positive/HER2-negative MBC receiving first-line CDK 4/6i. ResultsAmong 3832 patients enrolled in the GIM14-BIOMETA study, 701 were eligible. At a median follow-up of 24.80 months, no significant differences were found between HER2-zero and HER2-low subgroups in terms of first-line time to treatment discontinuation (TTD) (26.16 months [IQR 12.84-NR] vs. 27.60 months [IQR 12.12–64.44], p = 0.972) or overall survival (OS) (mOS>60 months for both groups, p = 0.398). Median TTD was 33.24 months (IQR 16.32-NR) for the endocrine sensitive subgroup, 19.92 months (IQR 8.88–51.24) for the secondary endocrine resistant subgroup and 17.40 months (IQR 7.44–24.72) for the primary endocrine resistant subset, respectively (p < 0.001). Among 239 patients receiving second-line treatment, no significant difference (p = 0.188) was found in terms of second-line TTD between those treated with capecitabine (6.11 months, IQR 2.96–11.47), taxane-based chemotherapy (5.06 months, IQR 2.99–9.99), everolimus plus exemestane (5.39 months, IQR 2.53–9.03) or fulvestrant (6.44 months, IQR 3.38-NR). ConclusionsEndocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

Real-world outcomes in patients with brain metastases secondary to HR+/HER2- MBC treated with abemaciclib and local intracranial therapy.

Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) MBC with brain metastases diagnosis before abemaciclib initiation. A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2- MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date). Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively. In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). Among 93 patients selected, median age at index was 67years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3months (IQR 8.7-25.4months), and median time from end of 1L therapy to 1LM initiation was 35.0days (IQR 25.0-53.9days). Median TTD was 9.3months (95% CI 6.1-11.3months). Median TTNT was 12.9months (95% CI 11.5-19.0months). This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.

Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer

IntroductionWith multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States. MethodsA cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record–derived de-identified database were followed through April 2023. Time to treatment discontinuation (TTD) in 1L and 2L, TTD on 1L plus 2L sequential therapy (TTD2), and total time on sequential ALK TKI therapy (including beyond 2L) were evaluated. ResultsPatients (N=273) were followed up for a median duration of 28.9 months. Among patients who discontinued 1L therapy, 22% died after 1L discontinuation (median time from discontinuation to death, 4.0 months) without receiving 2L therapy. Median (95% confidence interval [CI]) TTD was 21.9 (15.2–25.8) and 7.3 (5.3–10.2) months in 1L and 2L, respectively. Median (95% CI) TTD2 was 29.4 (25.1–36.1) months and total time on sequential ALK TKI treatment was 28.0 (23.6–32.9) months. ConclusionsIn this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5 years. The high attrition rate from 1L to 2L and the longest clinical benefit observed with 1L therapy support using the drug with the longest 1L effectiveness up front in patients with ALK-positive advanced NSCLC.

Prescribers and patients drive maintenance therapy patterns in a community oncology practice: National guidelines versus the real-world experience

ObjectivePrevious studies have shown that first-line (1L) maintenance therapy (MT) with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab improves outcomes among patients with advanced ovarian cancer (OC); however, these treatments are underutilized. This study aimed to provide a real-world understanding of MTs among patients with advanced OC who received 1L platinum-based chemotherapy (PBC). MethodsA retrospective chart review using iKnowMed electronic health records to identify patients aged ≥18 years with advanced OC who initiated 1L PBC between January 1, 2018–December 31, 2020. Following 1L PBC, patients could have received MT or active surveillance (AS). Kaplan–Meier methods were used to estimate time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (OS). ResultsOf the 600 chart-reviewed patients included, 239 (39.8 %) received MT and 315 (52.5 %) received AS. Patients who were <65 years of age, or those with higher-stage disease or those who had received neoadjuvant treatment, were more likely to initiate MT than AS. Genetic testing rates were low across both cohorts. Median (95 % confidence interval [CI]) TTD for the MT cohort was 13.6 months (11.0, 21.2). Median (95 % CI) rwPFS was 26.9 months (21.3, not reached) and 11.3 months (9.5, 13.0) for the 1L MT and AS cohorts, respectively (p < 0.0001). OS at 36 months was 82.4 % in the 1L MT cohort and 58.0 % in the 1L AS cohort. ConclusionsThis study reinforces clinical trial findings that 1L MT improves outcomes in patients with advanced OC; however, genetic testing rates and 1L MT remained low.

Real-world Bruton tyrosine kinase inhibitor (BTKi) treatment patterns and outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in US community oncology practices.

e19020 Background: BTKi therapies are standard of care for CLL/SLL, with acalabrutinib (acala) and zanubrutinib (zanu) having improved safety profiles vs ibrutinib (ibru). This study assessed real-world clinical characteristics, treatment patterns, and adverse events (AEs) among BTKi-treated patients with CLL/SLL. Methods: This is a retrospective observational study, updated with 5 months of additional data from a previous analysis. Adults in the US community oncology setting initiated BTKi treatment between Jan 1, 2020, and Jul 31, 2023, and were followed to Oct 31, 2023. De-identified structured electronic health records were analyzed from the Integra Connect-PrecisionQ real-world database. Cardiovascular (CV) AEs (based on ICD codes), time to treatment discontinuation (TTD), and time to next treatment (TTNT) were reported. Results: A total of 3064 patients initiated BTKi therapies during the index period (1L n=2815; 2L+ n=249). Median age (range) was 72 years (33-90) in 1L and 72 years (42-89) in 2L+. There were 63.1% and 65.5% males in 1L and 2L+, respectively. In 1L, 49.3% of patients were treated with ibru, 43.4% with acala, and 7.2% with zanu. Similar trends were observed for 2L+. More patients experienced CV AEs among those who received 1L ibru vs acala or zanu; 12.1%, 7.6%, and 7.3% at month 6 ( P&lt;0.05) and 14.6%, 9.4%, and 8.5% at month 9 ( P&lt;0.05). With longer follow-up, there was a trend for a more favorable CV safety profile for zanu. Of patients treated with 1L ibru, 12.7% discontinued ibru and switched to acala or zanu. Median TTD in 1L was shorter for ibru than acala or zanu (Table). The associated probability of remaining on treatment was higher with zanu vs ibru or acala at months 6 and 12 (Table). Median TTNT was not reached for zanu, while it was 30.2 months for ibru and 35.8 months for acala. Conclusions: While zanu had relatively smaller sample size and shorter follow-up, this study demonstrated better real-world safety and efficacy outcomes for acala and zanu vs ibru. Additional research is needed to explain and validate observed differences favoring zanu over acala. [Table: see text]

Effectiveness and safety of first-line serplulimab in patients with metastatic/locally advanced esophageal carcinoma (EC): A real-world study.

e16044 Background: The prognosis of metastatic/locally advanced EC has significantly improved with the development of immune checkpoint inhibitors. Serplulimab has been approved in the treatment of various solid tumors (e.g. esophageal squamous cell carcinoma [ESCC], small cell lung cancer). Considering the lack of real-world evidence, this study aimed to explore the real-world effectiveness and safety of serplulimab as first-line therapy in patients with metastatic/locally advanced EC. Methods: Thismulticenterretrospective study included patients with metastatic/locally advanced EC who received first-line serplulimab-containing therapy from March 2022 to December 2023. The demographic and disease characteristics, chemotherapy regimens selected by physicians, treatment response and adverse events were collected from medical record. The outcomes included progression free survival (PFS), objective response rate (ORR), overall survival (OS), duration of response (DoR), time to treatment discontinuation (TTD) and safety. Results: A total of 57 patients were included, 45 (78.9%) were male with a mean age of 68 years. A majority of patients had ESCC (n=40, 70.2%) and metastatic disease (n=35, 61.4%). The most common chemotherapy regimens combined with serplulimab were paclitaxel plus cisplatin (n=27, 39.1%) and etoposide and platinum (n=13, 23.6%). With a median follow-up of 4.8 month (range: 0.7-19.7), the median PFS was 7.4 months (95% confidence interval [CI]: 3.7-11.1). The ORR and DCR were 22.8% and 96.5% in all patients, respectively. The median DoR and TTD were 4.7 months (95% CI: 4.3-not estimated [NE]) and 13.9 months (95% CI: 3.6-24.1), respectively, while the median OS was not reached (NR). The mPFS was 11.1 months (95% CI: 7.0-NE) in patients with ESCC, which was numerically longer than those with neuroendocrine carcinoma (6.5 months, 95% CI: 5.8-7.3, P=0.052). Other effectiveness outcomes in ESCC are presented in Table. Patients &gt; 65 years had a significant improved mPFS compare to those ≤ 65 years (5.9 vs. 11.1 months, P=0.001). The rate of any grade adverse events (AEs) was 26.3% (n=15), while grade 3 or higher AEs was 10.5% (n=6), thrombocytopenia (7.0%, n=4), myelosuppression and pulmonary infection (both 5.3%, n=3) being the most common. Conclusions: First-line serplulimab combined with chemotherapy demonstrated promising effectiveness and favorable safety profile in patients with metastatic/locally advanced EC, especially in ESCC. The current real-world evidence indicates that serplulimab combined with chemotherapy could provide survival benefit for patients with advanced first-line EC. [Table: see text]

First-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations

IntroductionUp to 20% of EGFR-mutated NSCLC cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. MethodsPatients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). ResultsThirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10–15), 22 months (95% CI: 17–32) and 36 months (95% CI, 29–48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10–15), median TTD was 19 months (95% CI: 17–38), and median OS was 48 months (95% CI: 25–not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5–22), median TTD of 26 months (95% CI: 5–36), and median OS of 36 months (95% CI: 20–46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression. ConclusionsOsimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.

Abstract PO1-17-09: Real-world clinical outcomes in US patients with brain metastases secondary to HR+/HER2- metastatic breast cancer treated with abemaciclib

Abstract Background: Abemaciclib has demonstrated pharmacologically relevant intracranial concentrations and antitumor activity in patients with brain metastases secondary to HR+/HER2- metastatic breast cancer (MBC). However, clinical data is limited, and further assessments are warranted. This retrospective study describes real-world outcomes following abemaciclib initiation in patients with brain metastases secondary to HR+/HER2- MBC. Methods: Data were accessed from the US nationwide Flatiron Health electronic health records-derived de-identified database from 01/01/2011 to 12/31/2021. This real-world study included adult patients with a diagnosis of HR+/HER2- MBC with brain metastases prior to abemaciclib initiation. Patient and treatment characteristics were summarized using descriptive statistics. Kaplan-Meier methods were used to assess clinical outcomes from abemaciclib initiation: time to treatment discontinuation (TTD), progression-free survival (rwPFS), overall survival (rwOS). Intracranial rw best responses were also reported. Results: This study included 82 patients (one male) diagnosed with MBC and brain metastases prior to abemaciclib initiation and the median follow-up was 12.8 months. At data cut-off, 17 (20.7%) patients remained on abemaciclib therapy. Twenty-three (28%) patients received abemaciclib as the first line of therapy for MBC. Of the 82 patients in the study, 68 (82.9%) patients used concomitant endocrine therapy. Prior to abemaciclib initiation, 25 (30.5%) patients received chemotherapy and 33 (40.2%) patients received a CDK4 and 6 inhibitor. Most patients (67.1%) initiated abemaciclib at a dose of 150 mg twice daily. The median time from diagnosis of brain metastasis to abemaciclib initiation was 2.1 months (interquartile range:1.0, 8.0); 16 (19.5%) did not undergo surgical resection or receive radiation to the brain during this time. Sixty-six (80.5%) patients received brain radiation of which 56.1% received stereotactic radiosurgery (SRS) and 47.0% received whole-brain radiation (WBRT) either alone or in combination with craniotomy/metastasectomy, intrathecal chemotherapy, or surgery. The median TTD for abemaciclib was 7.1 months (95% confidence interval [95% CI]: 4.6, 11.3); most common reasons for discontinuation were disease progression (39.0%) or adverse events (29.3%). The median rwPFS was 9.2 months (95% CI: 6.0, 11.6) and median rwOS was 20.8 months (95% CI: 13.9, 26.0). Of the patients where response data were available (n = 51), rw intracranial clinical benefit rate (CBR; complete response [CR]/partial response [PR]/stable disease [SD] ≥24 weeks of abemaciclib initiation) was 62.7% (Table 1). Conclusion: In this real-world study, most patients with brain metastases secondary to HR+/HER2- MBC who initiated abemaciclib treatment received SRS or WBRT prior to or concurrent with abemaciclib initiation. While the clinical outcomes, rwPFS and intracranial CBR were encouraging, these findings should be interpreted with caution due to the nature of the real-world study design. Table 1. Intracranial Real-World Best Responses Citation Format: Wambui Gathirua-Mwangi, Holly Martin, Dan He, Shen Zheng, Kristin Sheffield, Jincy John, Sarah Rybowski, Priscilla Brastianos. Real-world clinical outcomes in US patients with brain metastases secondary to HR+/HER2- metastatic breast cancer treated with abemaciclib [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 PO1-17-09.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries

Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice.

Osimertinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that is used for first-line therapy in EGFR mutated non-small cell lung cancer (NSCLC) based on the results of the randomized FLAURA trial (ClinicalTrials.gov number NCT02296125). We performed a retrospective analysis of baseline characteristics and clinical outcomes in 56 real-world patients treated with osimertinib. In total, 45% of patients were determined to be FLAURA-eligible and 55% were FLAURA-ineligible based on the published inclusion/exclusion criteria of the aforementioned trial. For clinical outcomes, the median osimertinib time to treatment discontinuation (TTD) for all patients was 16.9 months (95% CI: 12.6-35.1), whereas the median TTD was 31.1 months (95% CI: 14.9-not reached) in the FLAURA-eligible cohort and the median TTD was 12.2 months (95% CI: 8.1-34.6 months) in the FLAURA-ineligible cohort. Re-biopsy at acquired resistance disclosed both on- and off-target mechanisms. The most common therapies following osimertinib included local therapies followed by post-progression osimertinib, platinum-doublet chemotherapy with or without osimertinib, and osimertinib combinatory targeted therapies. The median overall survival for all patients was 32.0 months (95% CI: 15.7-not reached), the median survival was not reached for the FLAURA-eligible cohort, and it was 16.5 months for the FLAURA-ineligible cohort. Our data support the use of osimertinib in real-word settings and highlight the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice. It is yet to be determined if the use of evolving first-line EGFR inhibitor combination strategies (either platinum-doublet chemotherapy plus osimertinib or amivantamab plus lazertinib) will similarly translate from clinical trials to real-word settings.

Real-World Treatment Patterns and Clinical Outcomes After Platinum-Doublet Chemotherapy and Immunotherapy in Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in the United States, Europe, and Japan.

To characterize treatment patterns and real-world clinical outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) who developed progression on an anti-PD-1/anti-PD-L1, herein referred to as anti-PD-(L)1, and platinum-doublet chemotherapy. Eligible oncologists/pulmonologists in the United States, Europe (France, Germany, and United Kingdom), and Japan completed electronic case report forms for patients with mNSCLC (no evidence of EGFR/ALK/ROS1 alterations). Eligible patients had disease progression on/after an anti-PD-(L)1 and platinum-doublet chemotherapy (received concurrently or sequentially), initiated a subsequent line of therapy (LOT) between 2017 and 2021, and had an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at this subsequent LOT initiation (index date). Overall survival (OS), time to treatment discontinuation (TTD), and real-world progression-free survival (rwPFS) after index were assessed using Kaplan-Meier analysis. Overall, 160 physicians (academic, 54.4%; community, 45.6%) provided deidentified data from 487 patient charts (United States, 141; Europe, 218; Japan, 128; at mNSCLC diagnosis: median age 66 years, 64.7% male, 81.3% nonsquamous, 86.2% de novo mNSCLC; at line of interest initiation: 86.0% ECOG 0-1, 39.6% liver metastases, 18.9% brain metastases, 79.1% smoking history). The most common treatment regimens upon progression after anti-PD-(L)1/platinum-doublet chemotherapy were nonplatinum chemotherapy (50.5%), nonplatinum chemotherapy plus vascular endothelial growth factor receptor inhibitor (12.9%), and platinum-doublet chemotherapy (6.6%). Median OS was 8.8 months (squamous, 7.8 months; nonsquamous, 9.5 months). Median TTD was 4.3 months (squamous, 4.1 months; nonsquamous, 4.3 months). Median rwPFS was 5.1 months (squamous, 4.6 months; nonsquamous, 5.4 months). In this multiregional, real-world analysis of pooled patient chart data, patients with mNSCLC who had disease progression after anti-PD-(L)1/platinum-doublet chemotherapy had poor clinical outcomes with various treatment regimens, demonstrating an unmet clinical need for effective options after failure on anti-PD-(L)1 and platinum-doublet chemotherapy treatments.

Real-world treatment patterns and outcomes in patients with mCRC by MMR/MSI status.

52 Background: There are limited data on real-world (RW) treatment patterns and outcomes in patients (pts) with metastatic colorectal cancer (mCRC), especially those with deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) disease, as they progress through lines of therapy. Methods: Data were extracted from the Flatiron Health electronic health record-derived database. Pts aged ≥18 years diagnosed with mCRC and with ≥2 clinical visits between January 01, 2013 and October 31, 2022 were included. Treatment patterns by therapeutic category and specific agent/regimens were explored across 3 time periods anchored to the start date of first line (1L): years &lt;2017, 2017–2019 and ≥2020 for pts both with dMMR/MSI-H and proficient mismatch repair (pMMR)/microsatellite stability (MSS) disease. Analyzed outcomes, by treatment category, included overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT). Descriptive statistics and Kaplan–Meier analyses were conducted. Results: A total of 34,853 pts with mCRC were identified; 24,622 pts (70.6%) were tested for MMR or MSI status, of whom 1,594 (6.5%) were dMMR or MSI-H. After applying key eligibility criteria, 938 dMMR/MSI-H and 12,305 pMMR/MSS pts were included. Overall, chemotherapy-based treatment was the most common treatment category given to pts, but the use of immuno-oncology (IO) agents increased over time. In the dMRR/MSI-H cohort, IO was the most commonly used treatment in 1L and 2L after 2020, driven largely by the use of pembrolizumab. The median OS (mOS) from start of 1L, irrespective of treatment type, was 30.30 months (95% confidence interval [CI]: 24.47, 34.41) in the dMMR/MSI-H cohort and 23.78 months (95% CI: 23.32, 24.34) in the pMMR/MSS cohort. For pts with dMMR/MSI-H, those receiving 1L IO had a mOS of 57.60 months (95% CI: 42.43, not reached [NR]). In pts who had IO after 1L-chemotherapy alone or chemotherapy + targeted treatment, mOS was 52.63 months (95% CI: 38.06, NR) and 59.61 months (95% CI: 34.41, NR), respectively. In pMMR/MSS pts, chemotherapy alone or chemotherapy + targeted treatment had the longest OS when received as 1L-therapy, at 23.88 months (95% CI: 22.89, 25.10) and 24.28 months (95% CI: 23.55, 25.10), respectively. The median TTD and TTNT from start date of 1L, irrespective of treatment type, were 4.90 months (95% CI: 4.28, 5.20) and 7.96 months (95% CI: 7.04, 8.78), respectively, in the dMRR/MSI-H cohort, and 5.79 months (95% CI: 5.72, 5.95) and 10.33 months (95% CI: 10.07, 10.59) in the pMMR/MSS cohort. Conclusions: These real-world data from over 10,000 pts with mCRC supplement findings from clinical trials and limited reported RW evidence. While IO demonstrates significant improvement for pts with dMMR/MSI-H, and mOS is similar regardless of whether IO is given in the 1L or later setting, there remains a high unmet need in pMMR/MSS for additional effective treatment options.

Real-World Treatment Patterns and Outcomes of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma Treated in US Oncology Practices.

Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US. This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018-2021). A clinical trial-like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan-Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort. The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6-9.0) months and 16.4 (13.3-21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8-29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age <60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status <3-4 (HR range, 0.13-0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without. These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.

Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis

BackgroundDry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.MethodsThis real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.ResultsOverall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).ConclusionsPatients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

Real-world (RW) use of niraparib (Nir) monotherapy (mono) as first-line (1L) switch maintenance (1LSM) therapy following chemotherapy (CT) plus bevacizumab (bev) induction treatment in patients (pts) with epithelial ovarian cancer (EOC) in the SW1TCH study.

536 Background: In the RW CHAR1ZMA study, 414 pts with EOC treated with 1L platinum-based CT (pbCT) and receiving 1L maintenance (1LM) nir mono had a median time to next treatment (TTNT) from end of 1L, a proxy for RW progression-free survival, of 13.3 mo (95% CI, 12.0–15.8 mo).1 Limited data exist on RW outcomes in pts with EOC who receive nir mono as 1LSM after 1L pbCT + bev treatment. The SW1TCH study describes nir mono use and outcomes as 1LSM therapy after 1L pbCT + bev treatment in a US RW setting. Methods: Using the nationwide Flatiron Health electronic health record–derived deidentified database, this retrospective observational study included pts ≥18 y of age at initial EOC diagnosis who received 1L pbCT + bev treatment followed by nir 1LM mono, initiated between Jan 1, 2017, and Sep 2, 2022. The index date was the initiation of nir 1LM. Pts were followed until the earliest of date of death, last activity, or end of study (Nov 30, 2022). Time to treatment discontinuation (TTD) and TTNT were estimated with Kaplan-Meier methods. Results: Of 93 pts selected, median age at index was 67 y (IQR, 60–72 y). Most pts had an Eastern Cooperative Oncology Group performance score of 0–1 (75.3%) and stage III/IV disease at diagnosis (89.2%). Overall, 86.0% of pts had BRCA wild-type EOC. 19.4% and 22.6% of pts had evidence of homologous recombination (HR)-deficient and HR-proficient EOC, respectively, whereas HR deficiency status was unknown for 58.1%. Median duration of 1L therapy was 4.8 mo (IQR, 3.6–6.0 mo), and median time from end of 1L pbCT to start of 1LM was 1.2 mo (IQR, 0.8–1.8 mo). Reasons for nir discontinuation are shown in the Table. Median TTD from index was 9.3 mo (95% CI, 6.0–11.3 mo). Median TTNT from end of 1L was 12.9 mo (95% CI, 11.5–19.0 mo). Conclusions: Observed results are consistent with CHAR1ZMA,1 suggesting the RW benefit of nir mono in 1LM regardless of bev use with1L pbCT. This RW study demonstrates that nir mono as 1LSM therapy is a viable treatment option for pts with advanced EOC.

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm.

Background: Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options following platinum-based chemotherapy and poor prognosis. The single-arm, Phase I GARNET trial (NCT02715284) previously reported dostarlimab efficacy in mismatch repair-deficient/microsatellite instability-high advanced or recurrent EC. Objectives: The objective of this study was to compare overall survival (OS) and describe time to treatment discontinuation (TTD) for dostarlimab (GARNET Cohort A1 safety population) with an equivalent real-world external control arm receiving non-anti-programmed death (PD)-1/PD-ligand (L)1/2 treatments (constructed using data from a nationwide electronic health record-derived de-identified database and applied GARNET eligibility criteria). Methods: Propensity scores constructed from prognostic factors, identified by literature review and clinical experts, were used for inverse probability of treatment weighting (IPTW). Kaplan-Meier curves were constructed and OS/TTD was estimated (Cox regression model was used to estimate the OS-adjusted hazard ratio). Results: Dostarlimab was associated with a 52% lower risk of death vs real-world treatments (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.66). IPTW-adjusted median OS for dostarlimab (N=143) was not estimable (95% CI, 19.4-not estimable) versus 13.1 months (95% CI, 8.3-15.9) for real-world treatments (N = 185). Median TTD was 11.7 months (95% CI, 6.0-38.7) for dostarlimab and 5.3 months (95% CI, 4.1-6.0) for the real-world cohort. Discussion: Consistent with previous analyses, patients treated with dostarlimab had significantly longer OS than patients in the US real-world cohort after adjusting for the lack of randomization using stabilized IPTW. Additionally, patients had a long TTD when treated with dostarlimab, suggesting a favorable tolerability profile. Conclusion: Patients with advanced or recurrent EC receiving dostarlimab in GARNET had significantly lower risk of death than those receiving real-world non-anti-PD-(L)1/2 treatments.

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm

Background: Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options following platinum-based chemotherapy and poor prognosis. The single-arm, Phase I GARNET trial (NCT02715284) previously reported dostarlimab efficacy in mismatch repair–deficient/microsatellite instability–high advanced or recurrent EC. Objectives: The objective of this study was to compare overall survival (OS) and describe time to treatment discontinuation (TTD) for dostarlimab (GARNET Cohort A1 safety population) with an equivalent real-world external control arm receiving non-anti-programmed death (PD)-1/PD-ligand (L)1/2 treatments (constructed using data from a nationwide electronic health record–derived de-identified database and applied GARNET eligibility criteria). Methods: Propensity scores constructed from prognostic factors, identified by literature review and clinical experts, were used for inverse probability of treatment weighting (IPTW). Kaplan-Meier curves were constructed and OS/TTD was estimated (Cox regression model was used to estimate the OS-adjusted hazard ratio). Results: Dostarlimab was associated with a 52% lower risk of death vs real-world treatments (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.66). IPTW-adjusted median OS for dostarlimab (N=143) was not estimable (95% CI, 19.4–not estimable) versus 13.1 months (95% CI, 8.3-15.9) for real-world treatments (N = 185). Median TTD was 11.7 months (95% CI, 6.0-38.7) for dostarlimab and 5.3 months (95% CI, 4.1-6.0) for the real-world cohort. Discussion: Consistent with previous analyses, patients treated with dostarlimab had significantly longer OS than patients in the US real-world cohort after adjusting for the lack of randomization using stabilized IPTW. Additionally, patients had a long TTD when treated with dostarlimab, suggesting a favorable tolerability profile. Conclusion: Patients with advanced or recurrent EC receiving dostarlimab in GARNET had significantly lower risk of death than those receiving real-world non-anti-PD-(L)1/2 treatments.

Retrospective observational study of outcomes in HER2-positive metastatic breast cancer patients treated with trastuzumab emtansine in single center.

15 Background: Trastuzumab emtansine (T-DM1) was established as a standard second line treatment option for metastatic HER2 positive breast cancer (mBC). However, the EMILIA study did not include disease progression patients who received pertuzumab plus trastuzumab previously. After CLEOPATRA study, the dual blockade treatment was indicated for advanced breast cancer as first line treatment. In this study, we attempted to build the T-DM1 predictive model and to evaluate the association between dual blockade and T-DM1 for metastatic HER2-positive breast cancer. Methods: This retrospective cohort study was conducted in Taiwan. Consecutive patients with metastatic HER2-positive breast cancer who had received T-DM1 between January 2013 and December 2022 were enrolled. Those patients were divided to two groups based on strategy of trastuzumab only or dual-blockade as prior therapy. Demographic, clinical, and pre- and post-T-DM1 treatment characteristics were described. The swimmer plots were used to estimate time to treatment discontinuation (TTD) and overall survival (OS). Results: Of 32 patients treated with T-DM1, 12 (38%) had prior treatment with pertuzumab plus trastuzumab. The median age was 60 years. Most patients had visceral disease and 59% had two or more prior treatments for mBC before T-DM1 (range 1–8 lines). Most patients (63%) stopped T-DM1 due to disease progressed and followed by financial problem (22%). In dual-blockade group, median TTD with T-DM1 was 4.5 months; median OS from diagnosis day was 68.2 months (8 patients still alive in the end of study). In trastuzumab only group, median TTD with T-DM1 was 3.8 months; median OS from diagnosis day was 73.2 months (5 patients still alive in the end of study). In our swimmer plots we found a trend that the shorter interval between trastuzumab +/- pertuzumab and T-DM1 the longer TTD with T-DM1. Conclusions: Patients treated with T-DM1 in this study appeared to have more advanced disease than patients in clinical trials and were treated in later lines of therapy. We should prescribe T-DM1 once trastuzumab with or without pertuzumab failure for the longer TTD. The small patient number was a major limitation in our study. A multi-center analysis is needed and it will help us for treatment suggestion under the Taiwan’s National Health Insurance clinical practice.

Real-world evidence of trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer using an administrative claims database in Japan

Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) are standard therapies for refractory metastatic colorectal cancer (mCRC). No results of large real-world data directly comparing FTD/TPI + bevacizumab (BEV) with FTD/TPI or REG monotherapy have been reported. We evaluated the efficacy and safety of FTD/TPI + BEV in a real-world setting. This retrospective study used a Japanese claims database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). Eligible patients were aged 20 years and over with a diagnosis of mCRC, and received their first dose of FTD/TPI or REG from 2014 to 2021. The primary endpoint was overall survival (OS) in a propensity score matching (PSM) population in which PSM was carried out by matching using a 1 : 1 ratio for the FTD/TPI+ BEV group and the control group (FTD/TPI or REG) by propensity score. To enhance robustness, sensitivity analyses of OS were carried out using the inverse probability treatment weighted (IPTW) approach and the analysis in the all eligible population. Secondary endpoints included time to treatment discontinuation (TTD), incidence of adverse events, and post-treatment. Eligible population was 2369 for the FTD/TPI+ BEV group and 9318 for the control group. The PSM population was 1787 for each group. Median OS (mOS) was longer in the FTD/TPI+ BEV group compared to the control group [17.0 versus 11.6 months, hazard ratio (HR)= 0.70, P < 0.001] in the PSM population. Similarly, mOS was longer for the FTD/TPI+ BEV group compared to that for the control group in IPTW analyses and in the all eligible population (both HRs= 0.68). Median TTD was 3.3 months for the FTD/TPI+ BEV group and 1.8 months for the control group in the PSM population (P < 0.001). Real-world data showed that FTD/TPI+ BEV was significantly associated with OS and TTD compared to FTD/TPI or REG. In clinical practice, FTD/TPI+ BEV can be a favorable regimen for refractory mCRC.