TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1–1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1–2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0–0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0–2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.
after 4 months 80.4AE17.3. Also, fatigue, appetite loss, and nausea/vomiting did not deteriorate over time. Final QoL results will be presented at the ESMO Congress.Conclusions: Overall survival in almost 500 patients from start of FTD/TPI is comparable to other population-based studies. Our results suggest that fewer symptoms at start of FTD/TPI treatment are associated with longer treatment duration. QoL was maintained during FTD/TPI treatment, which supports its use in clinical practice.Legal entity responsible for the study: The authors.
279 Background: Several therapies have recently gained regulatory approval in the United States (US) as second-line (2L) treatment options for patients with advanced unresectable or metastatic hepatocellular carcinoma (HCC). Treatment patterns and associated outcomes in a real-world population, especially in the contemporary era, remain understudied. Methods: This retrospective study utilized electronic health record data collected during routine patient care in outpatient oncology practices in the US. Adult patients diagnosed with advanced/ metastatic HCC between April 2017 and January 2020 were identified from the Concerto HealthAI database. Patients who survived at least one month from the end of first-line (1L) systemic therapy but did not initiate 2L therapy were classified as having received supportive care alone (SCA). Demographics, patient and disease characteristics, treatment patterns, and outcomes were described descriptively. Median overall survival (OS) from initiation of 2L therapy or end of 1L therapy for patients receiving SCA until death was estimated by the Kaplan-Meier method. Results: A total of 586 patients with advanced/ metastatic HCC were identified in the database. 330 patients received 1L therapy, and of those patients 63% (N= 207) received systemic 2L therapy (n= 105) or SCA (n= 102). At first diagnosis of advanced/ metastatic HCC, the median age was 64 years, and 86% were male. Of patients with ECOG status available at diagnosis (67%), 45% had ECOG status 0-1. The most common 1L agents prescribed were sorafenib (n= 126, 61%), lenvatinib (n= 28,14%) and sorafenib + nivolumab (n= 13, 6%) The most frequent agents prescribed in 2L were nivolumab (n= 44, 42%), sorafenib (n=18,17%), and lenvatinib (n=9, 9%). The median OS of patients receiving any systemic 2L therapy was 7.7 months (95% confidence interval 5.7-11.1) from time of receiving 2L therapy, whereas the median OS of patients receiving SCA was 5.0 months (95% confidence interval 3.3-7.1) from time of end of 1L therapy. Conclusions: In this contemporary national real-world cohort of patients with advanced/ metastatic HCC, a third of patients who received 1L therapy subsequently received 2L therapy. Next steps include investigating factors associated with non-receipt of 2L therapy, sequencing of therapies when multiple lines of therapies are received, and evaluating outcomes by type of agent received in 2L and beyond.
4146 Background: Elevated AFP in patients with aHCC is a poor prognostic factor with distinct molecular features, including high vascular endothelial growth factor (VEGF) signalling and increased angiogenesis. RAM, a human IgG1 monoclonal antibody, VEGF receptor 2 (VEGFR2) inhibitor, demonstrated improved survival vs placebo among patients with elevated AFP in the REACH-2 trial and is accepted as a standard of care for management of aHCC. We analyzed prognostic factors in patients with AFP ≥400 ng/mL and predictors of clinical benefit to RAM in an individual participant data (IPD) meta-analysis of the REACH and REACH-2 Phase III trials. Methods: Patients with aHCC, Child-Pugh A, ECOG performance status (PS) ≤1, and prior sorafenib were randomized (REACH 1:1; REACH-2 2:1) to RAM 8 mg/kg or Placebo Q2W. Meta-analysis was conducted in patients with AFP ≥400 ng/mL (n = 542). Univariate (UV) and multivariate (MV) analyses were performed using a Cox proportional hazard regression model. MV used the cut-off p-value < 0.1 from UV, irrespective of treatment arm. Overall survival (OS) was evaluated by Kaplan-Meier estimator and Cox models. To define predictors of RAM benefit, treatment-by-covariate interactions terms were evaluated. Results: In terms of prognosis assessed by MV analysis in patients with AFP ≥400 ng/mL, 6 variables among demographic and baseline disease characteristics were associated with poor OS in the RAM cohort (ECOG PS 1, AFP > 1000 ng/mL, Child-Pugh > A5, Extrahepatic site > 1, neutrophil-to-lymphocyte ratio > 3.2 and aspartate aminotransferase > 57 U/L) with an additional 3 factors identified within the whole cohort (macrovascular invasion presence, etiology HCV vs. Other and alkaline phosphatase ≥146). RAM benefit was present across all subgroups, including patients with very aggressive HCCs (AFP > 4000 ng/mL; HR: 0.64; 95% CI: 0.49-0.84) and those with nonalcoholic steatohepatitis /alcohol related aHCC (HR: 0.56; 95% CI: 0.40-0.79). Of note, two treatment-emergent (TE) events were the only factors that were significantly associated with improved RAM-related survival: TE-hypertension (p interaction = 0.0392) and TE-ascites (p interaction = 0.0001). However, these results should be interpreted with caution given that TE events are factors only observed after randomization. Conclusions: Several poor prognostic factors for OS were identified in patients with aHCC and elevated AFP. RAM provided an OS benefit irrespective of baseline prognostic covariates, with greater benefit observed in patients with aggressive HCC and those who experienced TE-hypertension or TE-ascites. Clinical trial information: NCT01140347; NCT02435433.
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