1L Setting Research Articles

Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC)

ObjectivesTo evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world. MethodsA US-based electronic health record–derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021, and September 30, 2022, and docetaxel between January 1, 2019, and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up. Treatment groups were balanced via overlap weighting propensity score methods. Median OS in the 2L and 2L+ settings were calculated using Kaplan-Meier estimates. Hazard ratios (HRs) were estimated via Cox proportional hazard models. ResultsOverall, the clinical characteristics in sotorasib and docetaxel cohorts were balanced after propensity score weighting. At baseline, most patients were > 65 years of age, had ECOG performance status of 0–1, were from the community practice setting, had advanced stage at initial diagnosis, and had prior anti-PD-(L)1 treatment and/or platinum-based chemotherapy. In the 2L setting, the median OS (95 % CI) for sotorasib (N=102) and docetaxel (N=58) patients was 10.2 (7.6–16.3) and 6.0 (4.2–11.0) months, respectively, with a corresponding mortality HR (95 % CI) of 0.62 (0.41–0.93). In the 2L+ setting, the median OS (95 % CI) for sotorasib (N=164) and docetaxel (N=116) was 10.2 (8.0–14.6) and 7.2 (5.1–10.6) months, respectively, with a corresponding mortality HR (95 % CI) of 0.65 (0.49–0.87). In patients with prior anti-PD-(L)1 treatment, the mortality HR (95 % CI) in the sotorasib group versus docetaxel was 0.61 (0.39–0.94) and 0.65 (0.48–0.89) in the 2L and 2L+ settings, respectively. Findings from other subgroups were consistent with the primary analyses. ConclusionIn this real-world comparative analysis of patients with pretreated KRAS G12C-mutated advanced NSCLC, sotorasib monotherapy demonstrated a longer median OS compared to docetaxel monotherapy or combination therapy.

505O Sotorasib (soto), panitumumab (pani) and FOLFIRI in the first-line (1L) setting for KRAS G12C–mutated metastatic colorectal cancer (mCRC): Safety and efficacy analysis from the phase Ib CodeBreaK 101 study

505O Sotorasib (soto), panitumumab (pani) and FOLFIRI in the first-line (1L) setting for KRAS G12C–mutated metastatic colorectal cancer (mCRC): Safety and efficacy analysis from the phase Ib CodeBreaK 101 study

359P Overall survival of palbociclib (PAL) + endocrine therapy (ET) in Japanese patients with hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the 1st line (1L) or 2nd line (2L) setting: A multicenter observational study

359P Overall survival of palbociclib (PAL) + endocrine therapy (ET) in Japanese patients with hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the 1st line (1L) or 2nd line (2L) setting: A multicenter observational study

Real-world use patterns, effectiveness, and tolerability of sacituzumab govitecan for second-line and later-line treatment of metastatic triple-negative breast cancer in the United States

PurposePatients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.MethodsThis retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described.ResultsThis analysis included 230 patients (median age 60 years, 26% Black, 17% with ECOG performance status ≥ 2, 66% in community settings; median of 2 prior lines of treatment in the metastatic setting); median follow-up was 7.2 months. Median (95% CI) real-world overall survival was 10.0 (8.3–11.1) months for all patients and 13.9 (9.8-not estimable) months in the 2L subgroup (n = 77). Granulocyte-colony stimulating factor (G-CSF) was administered concomitantly with SG in 134 (58%) patients; 35 (15%) received G-CSF for the first time. Median (IQR) time from SG start to G-CSF use was 8.5 (8.0–29.0) days. Seventeen (7%) patients discontinued SG due to toxicity.ConclusionsUsing a real-world, ethnically diverse population of patients with mTNBC presenting with poor prognosis, these data reinforced the findings from ASCENT. In routine clinical practice, SG is an effective treatment in the 2L setting, consistent with treatment guidelines.

Treatment (Tx) inequities in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) harboring actionable driver oncogenes (ADO) in the first-line (1L) setting.

e13673 Background: Targeted treatments (TT) have been approved for pts with mNSCLC harboring ADO in the 1L setting in recent years. This study aimed to understand if subpopulations of mNSCLC pts harboring ADO do not receive equitable access to guideline recommended 1L TT in US clinical settings. Methods: This retrospective study used the Flatiron Health electronic health record-derived, US nationwide, de-identified database. Pts with de novo mNSCLC (stage IVA or IVB) diagnosed between 4/1/2018-6/30/2023 were included if they were ≥18 y, had ≥2 visits after advanced diagnosis (aDx) and ≥90 days follow-up, received any biomarker testing prior to 1L Tx initiation, and harbored ADO (ALK, BRAF, EGFR, MET, NTRK, RET and/or ROS1). Results: Overall 2165 pts met study criteria: mean age was 67 y, 65% female, 11% Medicare insured, 58% commercial insured, 76% treated in the community setting with 11% Medicare and 64% commercial insured (vs 12% and 41% treated in the academic setting with Medicare and commercial insurance), and 45% had smoking history; of non-missing data, 12% had lowest socioeconomic status (SES), 26% with highest SES, 95% had non-squamous NSCLC, and 83% had ECOG performance status ≤1. The median time from aDx to testing result among the 53% non-Latinx (nL) white, 8% nL Black, 7% Latinx, 13% nL Asian, 7% nL other and 13% missing race/ethnicity was 21, 23, 24, 21, 23 and 20 days, respectively; median time from aDx to TT initiation was 38, 38, 43, 36, 47 and 37 days, respectively. Pts significantly more likely to receive 1L TT were (Table): pts of color vs white pts; Medicare vs commercial insurance at community sites; without vs with smoking history. Pts less likely to receive 1L TT were (Table): community vs academic sites; Medicare vs commercial insurance at academic sites. Consistent findings were seen in the 1817 pts with established 1L ADO (ie. ALK, EGFR or ROS1) (Table). Conclusions: When pts with mNSCLC harboring ADO had biomarker testing before Tx initiation, contrary to prior observed racial inequity in NGS testing, there was no racial inequity in receiving 1L TT. However, inequity in receiving 1L TT was observed by insurance type, smoking history and site of care. Interventions are warranted to address these contributors to 1L TT inequities. [Table: see text]

Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC): Subgroup analysis from TROPION-Lung02.

8617 Background: Dato-DXd is an antibody-drug conjugate (ADC) composed of an anti-TROP2 monoclonal antibody linked to a potent topoisomerase I inhibitor payload. We report updated findings from TROPION-Lung02 (NCT04526691) evaluating Dato-DXd plus pembro with or without Pt-CT as 1L therapy for aNSCLC. Methods: Patients (Pts) received Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with Pt-CT (triplet; cisplatin 75 mg/m2 or carboplatin AUC 5) Q3W across 6 cohorts. Pts in the expansion stage were primarily treatment (tx)-naïve. PD-L1 expression was evaluated by tumor proportion score (TPS < 50% or ≥50%) using immunohistochemistry (22C3 assay). The primary objectives were safety and tolerability, with efficacy a secondary objective. Results: 96 pts were treated with doublet (n = 42) or triplet (n = 54) therapy in the 1L setting. At data cutoff (Oct 31, 2023), 45% and 20% of pts receiving doublet or triplet tx were ongoing. Median age was 66 years in both subgroups. Median treatment durations were 6.6 and 5.8 months. Across doublet and triplet tx, the most common any-grade (Gr) treatment-emergent adverse events (TEAEs) were stomatitis (57%, 33%) and nausea (40%, 46%), mainly Gr 1–2. Gr ≥3 TEAEs were seen in 57% and 76% of pts; serious TEAEs in 38% and 44%. TEAEs associated with Dato-DXd discontinuation occurred in 29% and 39% of pts receiving doublet or triplet tx. TEAEs associated with death were seen in 2% and 9%, none considered related to study drug. Efficacy outcomes, including ORR and preliminary PFS, in the 1L setting overall and by PD-L1 status are summarized in the Table. Conclusions: As 1L therapy for aNSCLC, Dato-DXd plus pembro with or without Pt-CT continues to demonstrate durable antitumor activity. Efficacy was observed regardless of PD-L1 expression. Tolerability of the combinations was as expected based on known profiles of the individual agents, with no new safety signals observed. To date, this is the largest dataset reported for any ADC combined with an anti-PD-1/L1 agent in the 1L setting for aNSCLC. Clinical trial information: NCT04526691 . [Table: see text]

Real-world KRAS testing and treatment utilization among patients with metastatic non-small cell lung cancer.

e20593 Background: About 30% of patients with non-small cell lung cancer (NSCLC) have been reported to harbor gene mutations of Kirsten rat sarcoma oncogene homologue (KRAS). KRAS testing is recommended at metastatic NSCLC (mNSCLC) diagnosis and targeted treatment has shown better outcomes among KRAS-positive patients. This study aimed to understand KRAS testing rates among mNSCLC patients and utilization of targeted treatment among KRAS G12C positive patients treated in the community oncology setting. Methods: A random sample of 836 mNSCLC patients from the Integra Connect PrecisionQ de-identified database was included in this retrospective observational analysis, with additional information supplemented by chart curation. The database contains ~80% community oncology and ~20% academic practices with over 3 million cancer patients across 500 sites of care. Eligible patients were those aged ≥18 years, diagnosed with mNSCLC, and who initiated treatment in the second line (2L) setting between 01-May-2021 and 01-Jan-2024. KRAS testing rates and utilization of targeted treatment use were assessed and presented for this study. Results: The median (IQR) age of 836 mNSCLC patients was 68 (62,75) years; 52.9% were female; 73.8% identified as White, 11.7% as African American, 1.9% as Asian, and 12.6% as Other. Testing for KRAS was reported in 749 (89.6%) of the mNSCLC patients any time during the evaluation period, with most of them (738/749) tested before 2L treatment initiation; 186/749 (24.8%) of those patients were positive, and 74 were KRAS G12C positive. Of the KRAS G12C positive patients, 53/74 (71.6%) reported a targeted KRAS treatment in the 2L or greater setting. Conclusions: In this real-world setting, the testing rates for KRAS are almost 90%, with about 70% of the mutated patients receiving a targeted treatment. However, there is still a proportion of patients who did not receive KRAS testing or targeted treatment in this real-world setting. Appropriate and timely testing and utilization of the targeted treatment is necessary for better patient outcomes. [Table: see text]

A phase I/II trial of palbociclib, pembrolizumab, and endocrine therapy for patients with HR+/HER2- locally advanced or metastatic breast cancer (MBC): Clinical outcomes and stool microbial profiling.

1038 Background: Based on preclinical data highlighting synergy between CDK4/6 inhibitors and immune checkpoint inhibitors (ICIs), we conducted a phase I/II study of palbociclib, pembrolizumab, and endocrine therapy (ET) in pts with HR+/HER2- MBC. Given evidence suggesting a correlation between ICI response and stool microbiome composition in a wide array of cancers, we sought to determine if this biomarker could segregate responders in our cohort. Methods: Pts with stage IV HR+/HER2- MBC were enrolled and treated with palbociclib, pembrolizumab, and ET. Cohort 1 enrolled pts with stable disease on palbociclib + ET for at least 6 months. Cohort 2 and 3 enrolled pts in the first-line (1L) setting, with cohort 3 designed with a palbociclib + ET lead-in to evaluate the immune potentiating effect of palbociclib (not included in this report). The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Correlative studies assessed the association between the gut microbiome and response using previously published methods (1). Results: Between March 2017 and May 2022, 40 pts were accrued, with 4, 19 and 17 pts in cohorts 1, 2 and 3, respectively. There were 39 females and 1 male, with a median age of 51 (range 39-75). The ORR in cohorts 1, 2 and 3 were 2/4 (50%), 11/19 (58%) and 13/17 (76%), respectively. Median PFS across cohorts 2 and 3 (reflecting 1L therapy) was 25 mo (95% CI 21- not reached), and at a median follow-up of 35 mo, OS was 76% (95% CI 0.60-0.96). The most common grade 3/4 adverse events across all cohorts included neutropenia (83%), leukopenia (56%), elevated alanine aminotransferase (13%), elevated aspartate aminotransferase (13%), and thrombocytopenia (10%). Gut microbial profiling (total N=24 pts; Arm 2 N=7, Arm 3 N=17) demonstrated multiple species higher in abundance in pts with a response (p < 0.05), with notable species belonging to the families Lachnospiraceae, Ruminococcaceae, and Rikenellaceae. Several metabolic pathways were enriched in responders (p-value < 0.05), including pathways related to fatty acid biosynthesis and the tricarboxylic acid (TCA) cycle. Conclusions: Pembrolizumab added to palbociclib + ET in the 1L setting demonstrated a higher response rate compared to palbociclib + ET alone in HR+/HER2- MBC. Specific gut profiles were associated with response, with similar taxa of bacteria associated with ICI response in other tumor types (2). Enriched metabolic pathways may generate microbiota-derived metabolites that have an immunomodulatory effect. These results suggest that the gut microbiome may be associated with response to ICI combination therapy in MBC, which warrants further evaluation. 1. Dizman et al.,Nature Med 2022. 2. Spencer et al Science 2021. Clinical trial information: NCT02778685 .

Utilization of TAS-102 (TAS) or regorefenib (Rego) among commercially insured refractory metastatic colorectal cancer (R-mCRC) patients.

e23121 Background: R-mCRC is the time period after use of fluoropyrimidine, oxaliplatin, and irinotecan and usually in conjunction with biological therapies. Several agents are efficacious during R-mCRC with high level evidence for survival improvement. We describe access and utilization of therapeutics in this state using claims data. Methods: This is a retrospective cohort study using the Optum’s de-identified Clinformatics® Data Mart Database (2013-2020). We identified patients (pts) with mCRC after 2014; the metastasis date was set as the index date. Pts were required to have a continuous enrollment for 6 months pre- and 18 months post-index to ensure they were potentially in the refractory setting. Eligible pts were required to have utilization of standard therapies after diagnosis of metastatic disease. Those who switched from FOLFOX to FOLFIRI or vice versa were classified as refractory. The use of either TAS or Rego was identified during the entire follow-up period. Baseline characteristics were compared between patients who received TAS or Rego and those who did not using Chi-Squared test/T-test. We conducted multivariate logistic regressions to evaluate the factors associated with patients’ access to TAS or Rego. Results: 6,233 pts with mCRC identified, 53.7% male, and 70.4% white. FOLFOX was the dominant treatment in the 1L setting (60.1%). 9.7% received either TAS or Rego, with 4.8% taking Rego first and 4.9% receiving TAS first. Recipients of TAS or Rego were younger (mean age of 62.8 vs. 66.5, p < 0.001) and had fewer comorbidities (e.g. myocardial infarction was associated with reduced probability of receiving either TAS or Rego (p < 0.05)). More were enrolled in preferred provider organization in pts using these agents (45% vs. 37.5%, p < 0.001). In the multivariate analysis, Asian pts had a higher likelihood of using late-line therapies (OR = 1.53, p < 0.05). Among 707 pts who switched from FOLFOX to FOLFIRI or vice versa (R-mCRC), 29.8% received late-line therapy (15.7% TAS followed by Rego). The trends were similar among these patients. The TAS or Rego recipients were younger than the non-recipients (mean age of 60.6 vs. 63.8, p < 0.001), had fewer comorbidities, and enrolled in preferred provider organization (47.5% vs. 38.5%, p < 0.05). Conclusions: While front line therapy for mCRC is relatively homogenous, there is significant heterogeneity in transitioning and receiving later lines of therapy. This claims level analysis highlights the disparities in access to later lines of therapy. Further analyses for characterization of the patterns of care and disparities are underway.

Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Expanded efficacy analysis from CheckMate 8HW.

3503 Background: NIVO + IPI demonstrated superior progression-free survival (PFS) vs chemo in patients (pts) with previously untreated MSI-H/dMMR mCRC in the randomized phase 3 CheckMate 8HW study (NCT04008030). We report expanded efficacy analysis from the prespecified interim analysis of NIVO + IPI vs chemo in the 1L setting. Methods: Pts with unresectable or mCRC and MSI-H/dMMR status by local testing were enrolled across different lines of therapy and randomized 2:2:1 to NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), or chemo ± targeted therapies; treatments continued until disease progression or unacceptable toxicity (all arms) or for up to 2 years (NIVO ± IPI arms). In pts with blinded independent central review (BICR)–documented progression with chemo, crossover to NIVO + IPI was permitted. Dual primary endpoints were PFS by BICR per RECIST v1.1 for NIVO + IPI vs chemo (1L) and NIVO + IPI vs NIVO (all lines) in pts with centrally confirmed MSI-H/dMMR mCRC. PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death) was a key exploratory endpoint. Results: Among 303 pts randomized to NIVO + IPI (n = 202) or chemo (n = 101), 171 pts in the NIVO + IPI arm and 84 pts in the chemo arm had centrally confirmed MSI-H/dMMR. At 31.5-months (mo) median follow-up (range 6.1–48.4), NIVO + IPI demonstrated superior PFS vs chemo (HR 0.21; 97.91% CI 0.13–0.35; P < 0.0001). Subsequent systemic therapy was received by 20 (12%) and 57 (68%) pts in the NIVO + IPI and chemo arms, respectively. In the chemo arm, 56 (67%) pts received subsequent immunotherapy (39 [46%] crossed over to NIVO + IPI on study; 17 [20%] received non-study immunotherapy). Median PFS2 was not reached (NR) with NIVO + IPI and 29.9 mo with chemo (HR 0.27; 95% CI 0.17–0.44; Table). Any grade and grade 3/4 treatment-related adverse events (TRAEs) are presented (Table). Treatment-related deaths were reported for 2 pts in the NIVO + IPI arm. Conclusions: Clinical benefit with 1L NIVO + IPI vs chemo was maintained after subsequent therapy, as shown by improved PFS2 in pts with centrally confirmed MSI-H/dMMR mCRC. No new safety concerns were identified with NIVO + IPI. These results further support NIVO + IPI as a standard-of-care 1L treatment option for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . [Table: see text]

Creating a national model to build anti-cancer stewardship and quality improvement initiatives.

e23219 Background: The Department of Veterans Affairs (VA) Pharmacy Benefits Management (PBM) Services created a national stewardship with focus on anti-cancer therapeutics within a disease-specific cohort. Building a model to focus on Veterans with a common malignancy is a novel approach. A toolkit was built containing resources to support initiatives to promote standardization of practice and monitor outcomes as a continual quality improvement process. This model was piloted in Veteran patients with Chronic Myeloid Leukemia (CML) since Tyrosine Kinase Inhibitors (TKIs) account for the second highest utilization among outpatient oral anti-cancer therapies in VA . Methods: Business rules identified Veterans Integrated Service Network (VISN) CML cohorts by using data and diagnostic coding (ICD-10; SNOMED CT) from the VA Electronic Health Record (EHR): primary care and hematology/oncology visits, inpatient stays, and problem lists. Medication Use Evaluations (MUEs) were developed: MUE #1: Veterans who received a drug other than imatinib as their initial VA prescription If new initiation, documented reason(s) for drug selection If continuation, prior drug therapy history MUE #2: Veterans who switched from first to second-line TKI Documented reason(s) for switch to 2L Documentation of adverse drug reaction (ADR) in the EHR. Results: 16 VISNs participated in the MUEs. Patient counts are each ~25% of the total CML cohort; ~50% of patients received imatinib 1L and have not switched to 2L. Responses for MUE #1 (N = 559) 293 (52%) continued therapy originally started outside VA with 71% of these patients (n = 208) without documentation of prior imatinib 266 (48%) newly initiated therapy with top documented reasons Intermediate/high risk scoring: 109 (41%) Reason not documented: 80 (30%) Cited FDA indication for CML without clinical justification: 35 (13%) Responses for MUE #2 (N = 576) Top documented reasons for switch from 1L to 2L therapy ADR: 325 (56%) Resistance / inadequate response: 132 (23%) Disease progression: 117 (20%) Only 59 (18%) who experienced an ADR had it documented in the EHR allergies / adverse reactions section. Conclusions: Disease-focused oncology stewardship in a national healthcare system is feasible. Imatinib remains the preferred TKI and accounts for the highest utilization. Oncology Stewardship activities based on the results include education on disease coding, an educational document on why to use imatinib in the 1L setting, and a medication safety article to emphasize documentation of ADRs. In our 1L to 2L MUE, ADRs were the most common reason for patients to be switched to 2L. Future activities include an education sheet on managing TKI ADRs and criteria for a potential treatment-free remission. Further interventions in TKI prescribing may be instituted in select sites. Following initiatives for CML, Anti-Cancer Stewardship Program will be expanded to other oncologic diseases.

Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib/II dose escalation/expansion study.

6033 Background: Dual inhibition of PD-1 and LAG-3 is expected to synergistically increase immune response against tumor growth while chemotherapy can enhance the efficacy of immunotherapy through various mechanisms. Here we report the safety and efficacy of LBL-007 (anti-LAG-3) in combination with tislelizumab (anti-PD1) with or without chemotherapy in advanced solid tumors (Phase Ⅰb) and previously untreated patients with advanced nasopharyngeal carcinoma (NPC) (Phase II). Methods: In phase Ⅰb, patients with relapsed and refractory advanced solid tumor received LBL-007 (300 or 600 mg) plus tislelizumab (200 mg) (both i.v. Q3W), and in phase Ⅱ, patients with previously untreated recurrent or metastatic NPC patients received LBL-007 (600 mg) plus tislelizumab (200 mg) in combination with GC chemotherapy [gemcitabine (1000 mg/m2) and cisplatin (80mg/m2)] (i.v. Q3W). The primary endpoints were tolerability, safety, and efficacy. Results: Updated data with more follow up including duration of response and progression free survival will be available to report at the meeting. As of January 10, 2024, 21 patients (4 NPC, 7 NSCLC, 7 melanoma and 3 others) and 42 NPC patients were enrolled in in phase Ⅰb and phase Ⅱ respectively. The median follow-up was 13.1 months. During the study, no Dose limiting Toxicity (DLT) was observed, and Recommended Phase 2 Dose (RP2D) was determined to be 600mg Q3W for both chemo and chemo free regimens. In phase II, all grades TRAEs occurred in 39 patients (92.9%), with grade ≥3 TRAE in 24/42 patients (57.1%). The most common TRAEs (≥20%) included white blood cell count decreased, neutrophil count decreased, anaemia, ALT increased, AST increased, platelet count decreased, nausea, hyponatraemia, hypochloraemia, blood creatinine increased, vomiting, and hypothyroidism. Treatment interruption due to TEAEs occurred in 31 (73.8%) patients. 13 patients (31%) experienced SAEs. 1 patient experienced Grade 5 AE due to exacerbation of cachexia unrelated to LBL-007/tislelizumab. The clinical efficacy is shown in the table. Conclusions: LBL-007/tislelizumab combination is well-tolerated in patients with advanced malignant tumors. LBL-007/tislelizumab/GC combination showed manageable, no new safety concerns and encouraging antitumor activity in previously untreated and advanced NPC patients. The encouraging efficacy and safety profile may support a pivotal study with LBL-007 in combination with tislelizumab and GC chemotherapy for NPC development in 1L setting. Clinical trial information: NCT05516914 . [Table: see text]

HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results.

6005 Background: Treatment options are limited for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with no approved treatment specifically targeting human papillomavirus (HPV) 16-positive tumors. In the first-line (1L) R/M setting, only a minority of patients (~20%) respond to pembrolizumab monotherapy, including those with high programmed death ligand 1 (PD-L1) expression in the tumor. HB-200 comprises an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively. HB-200 vectors express a non-oncogenic HPV16 E7E6 fusion protein and induce E6 and E7-specific CD8 T-cell responses. Previously, we reported promising preliminary clinical activity of HB-200 in combination with pembrolizumab as 1L treatment for patients with HPV16+ PD-L1+ R/M HNSCC. Here, we report updated results with a focus on PD-L1 status. Methods: In this non-randomized Phase 2 part of the study, participants with HPV16+ PD-L1 combined positive score (CPS) ≥1 R/M HNSCC were treated with HB-200 intravenously (every 3 weeks [Q3W] then Q6W) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W). Safety, T cell response, and preliminary antitumor activity were assessed. Results: As of 12 January 2024, 42 patients with HPV16+ PD-L1+ R/M HNSCC (41 of oropharynx as primary cancer site) were treated with HB-200 plus pembrolizumab in the 1L setting. Median follow-up time was 5.6 months. Characteristics of this cohort included: median age 66 years (range 50-77), 41 (98%) male, 37 (88%) White, 14 (33%) with ≥ 10 pack/year smoking history, 40 (95%) check point inhibitor (CPI) naïve (2 received CPI in the adjuvant setting), and 21 (50%) with PD-L1 CPS ≥ 20. HB-200 + pembrolizumab were generally well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 6 (14%) patients, serious TRAEs in 3 (7%) patients, and TRAEs leading to treatment discontinuation in 2 (5%) patients. No treatment-related death were reported. Among 35 evaluable patients (those with ≥ 1 tumor response assessments), the overall response rate (ORR) was 43% (3 complete response [CR], 9 partial response [PR], 3 unconfirmed PR) and the disease control rate (DCR) was 71%. Notably, among patients with PD-L1 CPS ≥20 (N = 17), ORR was 59% (3 CR, 6 PR, 1 unconfirmed PR) and DCR was 88%. Conclusions: Updated data of HB-200 arenavirus-based immunotherapy plus pembrolizumab continued to demonstrate a favorable safety profile and promising clinical activity as 1L treatment in patients with HPV16+ PD-L1+ R/M HNSCC and confirms previously reported data. The results suggest that the subgroup of patients with PD-L1 CPS ≥20 may benefit more from this treatment, which warrants further development in a randomized pivotal study. Clinical trial# NCT04180215. Clinical trial information: NCT04180215 .

Real-world comparison of time to next treatment for patients with high-risk CLL/SLL in first line of treatment.

e19027 Background: The International Workshop on CLL recommends testing patients (pts) with CLL/SLL for deletion 17p (del17p) and tumor protein (TP) 53 mutations for prognosis and treatment decisions. Both Bruton Tyrosine Kinase inhibitors (BTKi) and B-cell lymphoma 2 protein inhibitor (BCL2i) are approved as effective frontline therapies for CLL/SLL pts, particularly those with high-risk features such as del17p and TP53. However, there is no clinical study directly comparing the efficacy of BTKi and BCL2i. We sought to understand the real-world use of BTKi and BCL2i as well as the differences in time to next treatment, a surrogate for progression-free survival, among CLL/SLL pts who were identified as having either del17p or TP53 mutations and treated with a BTKi or BCL2i in the 1L setting. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. We observed pts who started 1L treatment between 3/4/2016 and 12/4/2023. Risk status was captured via medical chart curation to determine the presence del17p or TP53 mutations. Time to next treatment was measured from the treatment start to the first of the initiation of a subsequent line of therapy or death. Descriptive analyses were used and time to next treatment was analyzed using a Kaplan Meier analysis. Results: We identified 295 CLL/SLL pts with high-risk features. The median (IQR) age of these pts at treatment start was 74 (66,81) years old, 62% were male, 77% identified as White, 8% as African American, and 15% as Other. Of these high-risk pts, 72% had only a deletion 17p, 13% had only TP53 mutation, and 15% had both. The percent of high-risk pts who received a BTKi in 1L was 69% with a median (IQR) age of 75 (65, 81) at treatment start, while 13% received a BCL2i in 1L with a median (IQR) age of 70 (64,77) at treatment start. The percent of pts who received neither a BTKi or BCL2i in 1L was 18% with median (IQR) age of 74 (68,80) at treatment start. The median time to next treatment for those who received a BTKi was 68.4 months (95% Confidence Interval [CI]: 48.4, NA) compared to 45.5 months (CI: NA, NA) for pts who received a BCL2i. The median (IQR) duration for patients treated with a BCL2i +/- obinutuzumab was 396 (285,603) days. The probability of pts who did not initiate a next treatment at 30 months was found to be 71% (95% CI, 64% to 78%) for those who received a BTKi (p <0.05) compared to 92% (95% CI, 83% to 100%) for those who received a BCL2i. Conclusions: The real-world data comparison of 1L treatment in high-risk pts with CLL/SLL shows that, after 30 months, the probability of not initiating the next treatment is 92% for those treated with a BCL2i compared to 76% for those treated with a BTKi. Additional follow-up and a larger sample may be needed to further validate these findings.

Surrogate endpoints and outcomes in modern small cell lung cancer trials.

8091 Background: Overall Survival (OS) may not always be a feasible primary endpoint. Endpoints such as Overall Response Rate (ORR), Disease Control Rate (DCR=CR+PR+SD), Progression Free Survival (PFS), are frequently used in the assessment of treatments. However, improvements in DCR, ORR, PFS may not translate into OS benefit. Resilient trial showed a doubling of ORR to PEGylated liposomal irinotecan1 compared to control but no improvement in PFS/OS. Furthermore, these associations may differ between 1st line (1L) and relapsed (2L) disease settings. This study analyzes the relationship between ORR, DCR, PFS, and OS in extensive-stage SCLC. Methods: MEDLINE, Embase, ClinicalTrials.gov were searched to identify randomized, phase III trials between 2014-2024. PRISMA guideline was followed. DCR, ORR, OS, PFS data were extracted. Weighted linear regression models investigated the association between treatment effects on DCR, ORR, OS, PFS. Weighted Pearson correlation analyses were performed under logarithmic transformation of DCR/ORR odds ratio besides DCR/ORR difference between treatment arms, with weights equal to the inverse of variance of DCR/ORR associated with the log PFS HR and the log OS HR. Logistic regression models were used to derive DCR/ORR odds ratios. Hazard ratios (HR) estimated from Cox proportional hazards regression models were used. All tests are two-sided; p-value < 0.05 is significant. Results: 115 trials were identified. 22 met the criteria. DCR: 1) 1L and 2L: DCR difference between arms and the log odds ratio and log PFS HR were strongly correlated: –0.63 (P = 0.001) for the DCR difference model; –0.64 (P = 0.0008) for the log odds ratio model. No correlation was found between DCR and OS; 2) 1L: No correlation between DCR and PFS & OS was found; 3) 2L: DCR difference between arms and the log odds ratio and log PFS HR were correlated: –0.84 (P = 0.01) for the DCR difference model; –0.84 (P = 0.01) for the log odds ratio model. ORR:1) 1L and 2L: ORR difference between arms and the log odds ratio and log PFS HR were correlated: –0.43 (P = 0.036) for the ORR difference model; –0.51 (P = 0.011) for the log odds ratio model; 2) 1L: No correlation between ORR and PFS & OS was found; 3) 2L: No correlation between ORR and PFS & OS was found. PFS:1)1L and 2L: The Pearson correlation coefficients between log HR of PFS and log HR of OS: 0.6 (p = 0.002); 2) 1L: The Pearson correlation coefficient between log HR of PFS and log HR of OS: 0.77 (p = 0.0005) 3) 2L: The Pearson correlation coefficients between log HR of PFS and log HR of OS: -0.14 (p = 0.732). Conclusions: In the 1L setting, neither DCR nor ORR predict PFS and OS. However, PFS predicts OS. In the 2L, ORR does not predict either OS or PFS; however, DCR predicts PFS and shows a trend with OS. Unlike in the frontline setting, PFS does not predict OS in the second-line setting. Reference: 1 Rudin CM, Dowlati A, Chen Y, et al.161O RESILIENT part 2: A randomized, open-label phase III study of liposomal irinotecan versus topotecan in adults with relapsed SCLC.

Real-world outcomes following adverse events and dose reduction of first-line ibrutinib in Medicare beneficiaries with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

e19017 Background: Dose reduction (DR) has been used to manage treatment-related adverse events (AEs) effectively and avoid early treatment discontinuation in patients (pts) with CLL/SLL receiving ibrutinib (ibr) in the first-line (1L) setting. This study evaluated DR and time to next treatment (TTNT) following AE in Medicare pts with CLL/SLL who were initiating ibr. Methods: Medicare Fee-for-Service (FFS) closed claims and enrollment data were used to identify pts with CLL/SLL who initiated 1L single-agent ibr (420 mg/day) from January 2014 to September 2020 with an incident AE following treatment initiation. Ibr DR was defined as reduction of starting dose following the first reported incident AE. Demographics, clinical characteristics, time to first incident AE, TTNT, and Healthcare Resource Utilization (HCRU) were analyzed among pts with and without DR (time to event measured in months). TTNT was defined as time from first incident AE to initiation of a new agent (≤90 days of ibr discontinuation) or death and was compared in pts with and without DR using Kaplan-Meier analysis and a time-varying Cox proportional hazards model. Results: Of 3575 pts included in the analysis (median age: 76 years; male: 63.4%), 459 (12.8%) had a DR. Duration of 1L ibr, time to first incident AE, time to DR, and TTNT varied among study cohorts. Median TTNT (standard deviation [SD]) for pts with and without DR was 49.8 months (1.4) and 22.0 months (0.6), respectively. After 6 and 12 months of follow-up, significantly fewer pts with DR discontinued treatment than pts without DR (6 months: 8.3% vs 27.3%, P = 0.0062; 12 months: 13.8% vs 38.2%, P = 0.0003). A total of 51 pts discontinued treatment immediately after the first incident AE; 414 deaths were reported within 90 days of the first incident AE. After controlling for baseline demographics and clinical characteristics as well as time-varying HCRU and costs, pts with DR were not significantly likely to discontinue treatment compared with pts without DR (hazard ratio [95% CI], DR vs no DR: 0.89 [0.71–1.12]). Increased age, comorbidity index score, healthcare costs, and number of hospitalizations were significant predictors of treatment discontinuation. Conclusions: Among Medicare FFS pts with CLL/SLL and an AE following initiation of 1L ibr, pts with DR remained on therapy significantly longer than pts without DR. Ibr DR may be an effective strategy to manage tolerability while maintaining clinical efficacy.

Phase 3 study of disitamab vedotin with pembrolizumab vs chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma that expresses HER2 (DV-001).

TPS4616 Background: Platinum-based chemotherapy (chemo) has been the standard first-line (1L) therapy for locally advanced or metastatic urothelial carcinoma (la/mUC). Recently, enfortumab vedotin, a nectin-4-directed antibody-drug conjugate (ADC) with a monomethyl auristatin E (MMAE) payload, plus pembrolizumab (pembro) showed improved survival over chemo. Human epidermal growth factor receptor 2 (HER2) expression (immunohistochemistry [IHC] 1+-3+) has been reported in approximately half of all patients (pts) across tumor types, including UC, and is a biomarker that may be associated with poor outcomes. Disitamab vedotin (DV; RC48-ADC) is an investigational ADC comprising a fully humanized HER2-directed monoclonal antibody, disitamab, conjugated to MMAE via a protease-cleavable mc-vc linker. DV elicits antitumor activity through multimodal mechanisms of action, including MMAE-mediated direct cytotoxicity, bystander effect, and immunogenic cell death. DV has shown encouraging activity with a manageable safety profile in pts with la/mUC—as a single agent in a HER2-expressing post-platinum setting (IHC 3+/2+; ORR, 50.5%; median [m]PFS, 5.9 months; mOS, 14.2 months) and in combination with a programmed cell death protein 1 (PD-1) inhibitor in all comers (ORR, 76.0% in treatment-naive pts; 83.3%, 64.3%, and 33.3% in HER2 IHC 3+/2+, IHC 1+, and IHC 0 subgroups, respectively). Improved outcomes observed with an MMAE payload plus PD-1 inhibition across the ADC landscape, along with DV data, provide a robust rationale for this phase 3 trial of DV with pembro in the 1L setting for HER2-expressing la/mUC. Methods: DV-001 (NCT05911295) is an open-label, randomized, multicenter, controlled phase 3 trial evaluating DV with pembro vs chemo in pts with previously untreated HER2-expressing la/mUC. Pts will be randomized 1:1 to Arm A or B. Pts in Arm A will receive DV IV every 2 weeks and pembro IV every 6 weeks. Treatment will continue until disease progression or intolerable toxicity; pembro will be administered for a maximum of 18 6-weekly infusions (approximately 2 years). Pts in Arm B will receive platinum-based chemo with gemcitabine IV on Days 1 and 8 of every 3-week cycle, and either cisplatin or carboplatin on Day 1 of every 3-week cycle for 4-6 cycles. Maintenance therapy with avelumab after completion of chemo may be given to eligible pts where approved and available. Pts must have previously untreated la/mUC, measurable disease per RECIST v1.1, ECOG PS of 0-2 and must be eligible for platinum-based chemo. HER2 expression must be determined using the VENTANA 4B5 HER2 IHC Assay centrally and using the most recent archival or fresh tumor sample. Primary endpoints include PFS per blinded independent central review and OS. Enrollment is ongoing in the US, Canada, and Australia and is planned globally. Clinical trial information: NCT05911295 .

Abstract PO3-16-11: Attrition rates from first- to third-line therapy in HER2+ metastatic breast cancer in Europe

Abstract Background: Patients (pts) with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (mBC) who experience progression with adjuvant first-line (1L) therapy (trastuzumab, pertuzumab, and a taxane) typically require treatment escalation. Trastuzumab emtansine was standard of care in the second-line (2L) setting until the recent approval (Jul 2022 in the EU) of trastuzumab deruxtecan in ≥2L settings. Receiving optimal targeted therapy in the earliest indicated setting is important to maximize the likelihood of durable clinical benefit. As new therapies become available, understanding subsequent lines of therapy may help guide treatment decision making and inform the optimal treatment paradigm for pts with HER2+ mBC. This study characterizes contemporary attrition rates in pts with HER2+ mBC receiving routine care in Europe. Methods: In this ongoing, multicenter, observational study, electronic medical record (EMR) data were collected from female pts ≥18 years old diagnosed with HER2+ mBC between Jan 1, 2017, and Jun 30, 2021, in the UK, France, Germany, Italy, and Spain. Structured EMR data and manually abstracted unstructured data from oncology centers were curated. Pts were followed for ≥12 months from mBC diagnosis. Data analysis is ongoing. The primary endpoint was attrition rate (percentage of pts who completed a line of therapy [LOT] but did not receive the subsequent LOT after 1L and 2L therapy). Documented reasons for attrition included death or move to end-of-life palliative care, end of study period, loss to follow up, or discontinuation due to toxicity. Reasons were categorized as ‘other’ if they did not meet these criteria, or if death or move to end-of-life palliative care occurred >30 days after treatment discontinuation. This abstract reports interim data from the UK, France, and Germany. Results: This interim analysis included data from 335 pts across five sites in three countries: two sites in the UK, one in France, and two in Germany (Table). Overall, 307 (91.6%) pts started 1L therapy and 172 (51.3%) pts started 2L therapy; overall attrition rates were 28.9% (70/242; 95% CI 23.3, 35.1) after 1L therapy and 33.1% (42/127; 95% CI 25.0, 42.0) after 2L therapy. The proportion of pts starting 1L and 2L therapy and attrition rates for each country are shown in the Table. Overall reasons for attrition were death (1L, n=28 [40.0%]; 2L, n=12 [28.6%]), move to end-of-life palliative care (1L, n=14 [20.0%]; 2L, n=5 [11.9%]), toxicity (1L, n=2 [2.9%]; 2L, n=1 [2.4%]), loss to follow up (1L, n=6 [8.6%]; 2L, n=4 [9.5%]), end of study period (1L, n=1 [1.4%]; 2L, n=4 [9.5%]), and other (1L, n=19 [27.1%]; 2L, n=16 [38.1%]). Further breakdown of results by country and hormone receptor (HR) status is shown in the Table. Conclusions: These data from routine clinical practice in the UK, France, and Germany indicate that a substantial proportion of pts with HER2+ mBC who completed 1L or 2L therapy did not receive a subsequent LOT (2L or 3L, respectively) for reasons other than death or move to end-of-life palliative care. Future analyses will focus on pooled and country-level treatment rates and real-world effectiveness. XX XX Citation Format: Peter Hall, Sue Cheeseman, Paul Cottu, Markus Krebs, Christian Scholz, Mahéva Vallet, Nicolas Niklas, Catherine Hogg, Markus Lucerna, Simon M Collin, Amanda Logue, Gráinne Long. Attrition rates from first- to third-line therapy in HER2+ metastatic breast cancer in Europe [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 PO3-16-11.

Abstract PO3-05-03: Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221)

Abstract Introduction: Endocrine therapy (ET) plus CDK 4/6 inhibitors is considered the standard of care as first-line therapy in hormone receptor positive (HR+)/HER2 negative (HER2-) metastatic breast cancer (mBC). Nonetheless, the use of chemotherapy (CT) is frequent in clinical practice, and access to CDK 4/6 inhibitors is limited in some countries. We used real-world data to describe treatment patterns, the impact of health insurance type, and outcomes among Brazilian patients with HR+/HER2- mBC treated in the first-line setting. Methods: In this observational retrospective study, female patients ≥ 18 years old diagnosed with de novo or recurrent HR+/HER2- mBC between January 2018 and December 2020 were included. Patients' data were extracted from medical charts or electronic health records (EHR). The primary endpoint was first-line treatment patterns in public and private health system cohorts. Key secondary endpoints were progression-free survival (PFS), defined as time from 1L treatment to progression or death, and overall survival (OS), defined as time from diagnosis of mBC until death or censoring. No formal statistical assumption was performed for sample size, the study recruited 2 cohorts of 150 patients from the public and 150 patients from the private health insurance system. Results: A total of 307 patients were included, 156 from public and 151 from private health insurance system, from 13 sites in Brazil. Median age was 56.8 (range 19.9-94.1), and 32.2% (N=99) had de novo MBC. Treatment patterns are described in Table 1. The most frequent treatment received in 1L was ET alone 42.4%, followed by CT (alone or CT followed by ET +- CDK4/6i) 31.6% and ET + CDK4/6i 25.1%. There was a significant difference between the 1L treatment with ET + CDK4/6i in the private and public systems, 48.3% vs 2.6%, p < .0001, respectively. The most frequently used CDK4/6i in 1L setting was Ribociclib (65.0%), followed by Palbociclib (36.9%) and Abemaciclib (7.1%). There was an increase in the use of CDK4/6i over time, 17% in 2018, 30.0% in 2019, and 27.9% in 2020. With a median follow-up of 32.2 months (95% CI: 29.4 - 34.4), the median 1L PFS was 22.9 months (95% CI: 16.9 - 25.2) in the public and 21.8 months (95% CI: 17.7 - 31.1) in the private health system, p=0.92. Median 1L PFS by treatment received was 13.6 months (95% CI: 6.1-39.0) with CT, 18.4 months (95% CI: 12.1-22.1) with CT followed by ET +-CDK4/6i, 21.9 months (95% CI: 17.3-25.5) with ET and 31.1 months with ET plus CDK 4/6i (95% CI: 15.8-42.8). Overall, median OS was 52.8 months (95%CI 49.4-NR). The 4-year OS rate per 1L treatment received were 50.3% (95% CI: 28.7-68.5) with CT, 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i, 74.4% (95% CI: 58.0-85.1) with ET alone, 71.3% (95% CI: 49.6-85.0) ET + CDK4/6i, 50.3% (95% CI: 28.7-68.5) with CT and 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i. Conclusion: ET is the most commonly used 1L treatment in clinical practice in Brazil, followed by ET + CDK4/6i and CT. A large difference in CDK4/6i use was observed between private and public health systems, reflecting the current limited access to CDK4/6i in Brazil. This study highlights treatment disparities within a nation with a fragmented health insurance system. Table 1. Treatment Patterns in Public and Private Healthcare Systems Citation Format: Gustavo Werutsky, Daniela Rosa, Tomás Reinert, Romualdo Barroso-Sousa, Heloísa Resende, Poliana Signorini, Eduardo Cronenberger, Juliana Góes Martins Fagundes, Jorge Henrique Santos Leal, Marina Dutra Giffoni, Aline Vieira, Luiza Nardin Weis, Jose Marcio Figueiredo, Tatiana Correa, Fernando Castilho Venero, Luisa Mostardeiro Tabajara Franche, Marina Musse Bernardes, Rafaela Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221) [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 PO3-05-03.

Abstract PO4-05-08: Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China

Abstract Background: Endocrine therapy resistance was classifed as primary and secondary, guiding the first-line (1L) treatment choices for hormone receptor positive, HER2-negative (HR+/Her2-) metastatic breast cancer (mBC). However, it is unknown whether it is primary ET resistance or not to the stage IV de novo patients. Therefore, We performed a retrospective study to predict primary resistance in advance in de novo patients and have a more appropriate treatment strategy. Methods: We identified newly diagnosed with stage IV de novo HR+/HER2- mBC patients received single-agent endocrine therapy (ET) or ET plus CDK4/6 inhibitors (CDK4/6i) in 1L setting from January 1, 2020 to Jun 30, 2022, using the National Cancer Information Database (NCID) in China. Primary ET resistance (PER) was defined as switching to second-line treatment within 6 months after receiving the 1L ET±CDK4/6i, whereas secondary ET resistance (SER) patients were those who received 1L ET±CDK4/6i treatment more than six months. The Chi-Square test was used to compare the baseline characteristics of PER and SER patients. Result: A total of 217 patients who met the inclusion criteria were included in the analysis, among which 161 patients received single-agent ET and 56 patients received ET plus CDK4/6i. 18.4% of the patients were classified as PER patients, whereas 81.6% showed SER patients. PER patients were younger (median age of 52 years vs. 58 years in SER patients, p=0.01). In terms of clinicopathological characteristics, patients with PER have a higher percentage of liver metastases (14/40 (35%) vs. 20/177 (11.3%) in SER, p< 0.01), distant lymph node metastases (19/40 (34%) vs. 45/177 (25.4%) in SER, p = 0.01), and bone metastases (30/40(75%) vs. 97/177(54.8%) in SER, p = 0.02). Furthermore, the PER rate was 21.7% (35/161) in patients received single-agent ET, compare with 8.9% (5/56) in ET plus CDK4/6i patients, p=0.04. Regarding the following treatment pattern in the PER patients, a high percentage of patients received chemotherapy, accounting for 50%, 30% still received another endocrine therapy, and the remaining 20% patients received CDK4/6i combined with endocrine therapy. Conclusions: There is still a significant proportion of de novo HR+/HER2- mBC patients with primary endocrine resistance, a relatively low proportion of PER in patients receiving endocrine in combination with CDK4/6i. Table. The proportion of primary endocrine resistance across treatment regimens in de novo HR+/HER2- metastatic breast Cancer Citation Format: Zhanhong Chen, Xiying Shao, Yabing Zheng, Wenming Cao, Junqing Chen, Weizhu Wu, Ting Wang, Xiaojia Wang. Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China [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 PO4-05-08.