Later Lines Of Therapy Research Articles

Dose Modifications in the Management of Chronic Phase Chronic Myeloid Leukemia: Who, What, and When.

With the availability of BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs), outcomes for most individuals with chronic phase chronic myeloid leukemia (CP-CML) are outstanding, with life expectancy similar to age-matched peers. Treatment-emergent adverse events (TEAEs) impair quality of life and many patients struggle with low-level chronic AEs, which for some individuals impact emotional well-being as well as social and work functioning. An emerging body of data supports that many TEAEs are related to therapy dose and can improve with dose reduction. However, it is critical that dose reductions do not alter current outcomes, especially in the rare patients who are at greater risk of losing response or transforming to acute leukemia. Organizations including the National Comprehensive Cancer Network have begun to address when dose reductions may be considered in patients with CP-CML. In this manuscript, we review retrospective and prospective data reporting outcomes in patients after dose reduction and review data supporting lower dose preemptive dosing in first-line and later-line therapy. Switching therapy for intolerance can result in improvements in symptoms and limit toxicity, but other TEAEs may occur. Additionally, emerging therapeutics such as the new class of BCR::ABL1 allosteric inhibitors are under evaluation with a goal of improving tolerability. However, with many TKIs on the cusp of becoming generic, dose reduction becomes an appealing and important cost-effective strategy to minimize TEAEs and improve quality of life while preserving outstanding outcomes in CP-CML.

Phase II Study of Irinotecan, Trifluridine/tipiracil (TAS-102) plus Bevacizumab as a Later-line Therapy for Patients with Metastatic Colorectal Cancer (mCRC): a prospective single-center explorative study.

To explore the efficacy and safety of the combination of irinotecan, trifluridine/tipiracil (TAS-102), and bevacizumab in a later-line setting for metastatic colorectal cancer (mCRC) patients. This was a single-center, phase II trial. The mCRC patients who are refractory to standard first-line and second-line treatment are eligible. Patients who previously received irinotecan while progressing during maintenance therapy are also eligible. The primary endpoint was the objective response rate (ORR). Between August 1, 2022, and September 30, 2023, 35 patients were enrolled, and 31 of them were evaluable for efficacy. The ORR was 25.8% (8/31), and the disease control rate (DCR) was 93.5% (29/31). As of April 30, 2024, the median progression-free survival (PFS) was 9.2 months (95% CI 6.285-12.115), whereas the median overall survival (OS) was not reached with the 1-year OS rate of 73.5%. The most common grade 3/4 treatment-related adverse events were neutropenia (34.3%), anemia (17.1%), and thrombocytopenia (8.6%). Irinotecan, TAS-102 plus bevacizumab regimen preliminarily demonstrated promising efficacy with tolerable toxicity for mCRC patients as later-line treatment. This regimen warrants further exploration in refractory mCRC patients.

P2-1 Real-world clinical outcomes of nivolumab as a second- or later-line therapy for esophageal squamous cell carcinoma

P2-1 Real-world clinical outcomes of nivolumab as a second- or later-line therapy for esophageal squamous cell carcinoma

Abstract C002: A pilot study to assess the safety, tolerability, and tumor responses with lenvatinib plus pembrolizumab in patients with advanced pancreatic ductal adenocarcinoma in second-line or later of treatment

Abstract Introduction Lenvatinib plus PD-1 inhibition substantially decreases tumor-associated macrophages and increases infiltration of CD8+ T-cells in mouse tumor models, enhancing anti- tumor activity, thus providing the background rationale to explore the clinical response and the safety of the combination of lenvatinib plus pembrolizumab in patients with pancreatic cancer. Methods Patients with metastatic pancreatic adenocarcinoma with disease progression on ≥ 1 line of systemic therapy were eligible for screening. Eligible patients received therapy on a 42 day cycle, receiving fixed doses of 400mg of pembrolizumab on day 1 and 20mg of lenvatinib daily. Blood and tumor tissue were collected to evaluate molecular determinants of response and changes in the tumor’s T-cell composition. Results Fifteen patients received treatment on protocol, with a median of 1 cycle of treatment. Of these 15 patients, 5 were female and 10 were male; 12 enrolled at a performance status of 0 and 3 at a 1; 10 had one prior line of therapy in the metastatic setting and 5 had 2 lines. Currently, 1 patient remains on protocol after 3 cycles of therapy; 3 other patients who had disease progression on protocol remain alive at the time of this submission and are on other treatments. While no tumor responses were observed on therapy, 7 patients had stable disease and remained on treatment beyond 1 cycle of therapy. In 3 of these 7 patients, CA 19-9 trend was consistent with cancer control (1 additional patient was a nonproducer). The disease control rate was 47% and the median progression free survival was 10 weeks [95% CI, 6.3 – 11.7]. Median overall survival was 19.8 weeks [95% CI, 13.5 – 26.1]. All 14 patients who discontinued therapy did so due to disease progression; none stopped therapy due to treatment related toxicity. Four patients had either lenvatinib dose delays or reductions per protocol due to toxicity; no patients had dose delays/modifications to the pembrolizumab. No unexpected adverse events were experienced. The most frequently occurring toxicities of any grade were fatigue (8), hypertension (7), proteinuria (6), nausea (4), hypothyroidism (4), mucositis (4), and hyponatremia (4). There was one occurrence of each of the following serious adverse events, with noted CTCAE grade (Gr) and attribution to therapy: sepsis (Gr3, unrelated), immune mediated endocrinopathy (Gr3, possibly related), hypotension (Gr3, possibly related), fatigue (Gr3, unrelated), lung infection (Gr3, probably related), enterocolitis (Gr3, probably related), fever (Gr3, possibly related). There were no grade 4 or 5 events. Conclusions The combination of pembrolizumab with lenvatinib demonstrated pancreatic cancer control which, while modest, is appreciated in this later line of therapy where few treatment options exist. These benefits were achieved while being a safe and manageable treatment for patients. Blood and tissue data will offer further insights into tumor responses, and combination of this therapy with chemotherapy and in an earlier line of treatment is being explored. Citation Format: Brandon G Smaglo, Ryan Sun, Shubham Pant, Michael S Lee, Dan Zhao, Phat H Le, Milind Javle, Jason A Willis, Christine Parseghian, Manoop Bhutani, Saman Chishty, Stacy Diao, Michael W Leung, Ryan W Huey, Maria Pia Morelli, Michael J Overman, Robert A Wolff. A pilot study to assess the safety, tolerability, and tumor responses with lenvatinib plus pembrolizumab in patients with advanced pancreatic ductal adenocarcinoma in second-line or later of treatment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C002.

The Usefulness of Serum Interleukin-6 as a Predictor of Response to Atezolizumab plus Bevacizumab Combination Treatment in Hepatocellular Carcinoma

Introduction: In atezolizumab plus bevacizumab (Atezo/Bev) combination treatment, both drugs act on the immune system. Previously, we reported that immunological changes after Atezo/Bev administration for unresectable hepatocellular carcinoma (uHCC) revealed significant alterations in interleukin (IL)-6, soluble IL-2 receptor, tumor necrosis factor-alpha, and programmed cell death-1 levels. Among these variable factors, serum levels of IL-6 can be easily measured on a commercial basis. Therefore, this study aimed to investigate the utility of serum IL-6 as a predictor of tumor response to Atezo/Bev treatment for uHCC. Method: The study included 44 patients with HCC treated with Atezo/Bev. Blood samples were collected before and 3 weeks after treatment, and tumor response was assessed using contrast-enhanced computed tomography 6 weeks after treatment. Results: Significant changes in serum IL-6 levels were observed in patients treated with Atezo/Bev as first-line therapy but not in those treated with it as second-line or later-line therapy. In patients treated with Atezo/Bev as first-line therapy, serum IL-6 levels increased significantly after treatment in patients with a complete or partial response but not in patients with stable or progressive disease. Furthermore, compared to other tumor markers such as alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-gamma-carboxyprothrombin, serum IL-6 levels exhibited the highest sensitivity in predicting tumor response during the treatment period. Conclusion: In patients with uHCC treated with Atezo/Bev, serum IL-6 levels could serve as a potential predictor of tumor response. Elevated levels after treatment may indicate a favorable tumor response and prognosis.

Real-World Data with CDK4/6 Inhibitors-A Single Center Experience from Croatia.

There are limited real-world data (RWD) regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in western Balkan. The aim of our study was thus to analyze factors influencing progression-free survival (PFS) and overall survival (OS), along with the differences in adverse effects of CDK 4/6 therapy in a tertiary healthcare center in Croatia. We evaluated medical and demographic data for 163 consecutive patients with metastatic breast cancer treated with CDK4/6 inhibitors for at least one month, from October 2018, after the drug became available in Croatia. Eligible patients in our study were those patients who were treated with palbociclib, ribociclib, or abemaciclib. The median PFS of CDK4/6 inhibitors treatment was 2.2 years (95% CI 1.8-3.3), with the longest ongoing treatment for 5.4 years. Treatment with CDK4/6 inhibitors in the first line was associated with a longer PFS compared to the second line or beyond (HR 0.50, 95% CI 0.3-0.9), and patients without liver metastasis exhibited longer survival compared to patients with liver metastasis (HR 0.46, 95% CI 0.2-0.8) (both p < 0.05). Regarding the choice of CDK4/6 inhibitors, ribociclib exhibited longer PFS compared to palbociclib (HR 0.49, 95% CI 0.29-0.82) (p = 0.0032), although the effect was not statistically significant when separating patients who were treated with CDK4/6 inhibitors in the first-line (HR 0.59, 95% CI 0.29-1.2), or second- or later-line therapy (0.49, 95% CI 0.15-1.55); the trend was present in both lines, however. The presence of liver metastasis (p = 0.04), initial luminal A grade (p = 0.039), and time to metastasis up to 5 years from the initial cancer (p = 0.002) were the only factors that remained statistically significant for PFS in multivariate analysis. Median OS since the diagnosis of metastatic disease was 4.5 years (95% CI 3.9-6.3), median OS since the start of CDK4/6 inhibitors treatment was 3.7 years (95% CI 3.4-4.4), while median OS from initial cancer diagnosis was 15.8 years (95% CI 13.8-18.3). There was no difference in OS based on the choice of CDK4/6 inhibitor (p = 0.44) or the adjuvant hormonal therapy (p = 0.12), although a nonsignificant trend for better OS with ribociclib was present for both regardless of whether it was in first- or second/later-line therapies (p > 0.05). In a multivariate analysis, only the presence of liver metastasis (p = 0.0003) and time to metastasis under 5 years from primary breast cancer (p = 0.03) were associated with a worse OS. Our study provides the RWD with the use of CDK4/6 inhibitors in the treatment of metastatic HR+/HER2- breast cancer. To our best knowledge, there are limited RWD regarding CDK 4/6 inhibitors use in western Balkan; thus, our study provides valuable data from everyday clinical practice for this region of Europe, bridging the gap between randomized clinical trials and clinical reality in western Balkan.

The use of immune checkpoint inhibitors in advanced gastric/gastroesophageal adenocarcinomas - real-world evidence and the use of alternative dosing.

Immune check point inhibitors (ICIs) have an established role in Microsatellite-Instability-High (MSI-H) and Combined Positive Score (CPS) high advanced gastric/gastroesophageal (G/GE) adenocarcinomas, but there is limited real world data with regard to practice patterns, and efficacy of standard doses (SD-ICIs) and alternative lower doses (LD-ICIs). A retrospective study of patients with advanced G/GE adenocarcinomas receiving ICIs was conducted. The primary endpoint of the study was 12-month overall survival (OS), which was computed by Kaplan-Meier method. A total of 91 patients were available for analysis during the study period. Seventy-four patients (81%) received nivolumab, while the remaining received pembrolizumab. Fifteen patients (16%) had MSI-H status and had a 12-month OS of 60% and median OS of 15 months (median follow-up - 38.3 months). In the Microsatellite-Stable (MSS) cohort (84%; n = 76), ICIs (combined with chemotherapy) were used predominantly in pre-treated patients (54%; n = 41). Patients with CPS ≥5 (72%; n = 55) had improved survival compared to patients with CPS <5 (28%; n = 21) (12-month OS: 52% vs. 26%; Median OS: 12.8 months vs. 3.2 months; p = 0.005). There was no difference in survival between patients who received SD-ICIs (54%; n = 41) and LD-ICIs (46%; n = 35) (12-month OS: 42% vs. 48%; Median OS: 8.7 months vs. 11 months; p = 0.44). Patients with advanced G/GEJ adenocarcinomas in the real world predominantly received ICIs during later lines of therapy as opposed to first line therapy. Using a CPS cutoff of ≥5 as opposed to CPS <5 predicts for improved survivals in MSS patients and patients receiving low dose ICIs have similar survival outcomes to patients receiving standard dose ICIs within the confines of a heterogenous study cohort.

Performance of Low-Dose Immunotherapy and Standard-Dose Immunotherapy in Microsatellite Instability-High Metastatic Colorectal Cancer: Real-World Data (CLouD-High Study).

Standard-dose immune checkpoint inhibitors (SD-ICIs) are the standard of care as initial therapy in microsatellite instable-high (MSI-H) advanced/metastatic colorectal adenocarcinomas (mCRC), but there are preclinical data to suggest that low-dose ICIs (LD-ICI) might also have similar efficacy. A retrospective study of patients with MSI-H mCRC receiving ICIs between June 2017 and January 2023 was conducted. The primary end point of the study was 12-month progression-free survival (PFS), which was computed using the Kaplan-Meier method. A total of 65 patients were available for analysis during the study period. Sixty patients (92%) received nivolumab, whereas the remaining received pembrolizumab. First-line ICIs were received by 18 patients (28%), whereas 47 patients (72%) received ICIs during later lines. Thirty patients (47%) received LD-ICIs (all received nivolumab), with the remaining receiving SD-ICIs (53%). At a median follow-up of 16.5 (95% CI, 11.8 to 21.2) months, median PFS was not reached in the entire cohort. The 12-month PFS rate in the LD-ICI cohort was 90%, whereas it was 75.8% in the SD-ICI cohort. There were no statistical differences in patients receiving ICIs as first-line therapy (12 months PFS-94.4%) or during later lines of therapy (12-month PFS-77.9%; P = .56). ICIs in the current study show survivals which are similar to those seen in seminal trials in patients with MSI-H mCRC. Low-dose ICIs appear to work in MSI-H mCRC and should be explored prospectively in clinical trials. Patients with MSI-H status should be exposed to ICIs, whether initially or later during treatment, whenever feasible.

Real‑world evidence of advanced non‑small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Safety and efficacy of flumatinib as later-line therapy in patients with chronic myeloid leukemia.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice.

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

Incidence of serious infections in the working-age Japanese adult population with rheumatoid arthritis treated with tumor necrosis factor-α inhibitors and interleukin-6 inhibitors: A nationwide retrospective cohort study.

This retrospective cohort study aimed to compare the risk of serious infections in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α inhibitors (TNFαi) and interleukin-6 inhibitors (IL-6i), with no prior use of biological disease-modifying antirheumatic drugs (bDMARDs). We employed the nationwide insurance claims database encompassing the years 2005 to 2018 in Japan. The inclusion criteria specified patients who were prescribed any type of bDMARDs, including TNFαi and IL-6i. The following exclusion criteria were applied: missing prescription dates, RA not diagnosed, below 16 years of age, bDMARDs prescribed within 6 months of registration, RA diagnosed post-bDMARDs prescription, and incidence of serious infections within 2 weeks before bDMARDs therapy. We applied stabilized inverse probability weights and utilized a Cox regression model to estimate the risk of serious infections associated with TNFαi and IL-6i. The cohort of 2493 patients with RA was categorized into a TNFαi group and an IL-6i group of 2018 and 475 participants, respectively. The median follow-up duration (interquartile range) was 347 (147-820) days in the TNFαi group and 369 (149-838) days in the IL-6i group. In the inverse probability-weighted cohort, the incidence rates (95% confidence interval) of serious infections were 2.13 (1.65-2.71) and 3.25 (2.15-4.69) per 100 person-years for the TNFαi and IL-6i groups, respectively. The hazard ratio (95% confidence interval) comparing the TNFαi group to the IL-6i group was 0.66 (0.36-1.20, p = 0.168). The results underscore the lack of evidence to preferentially favor either TNFαi or IL-6i as later-line therapy in the management of bDMARDs-naive RA to mitigate the risk of serious infections.

Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC). NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared. Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6months (95% CI 4.8 to 6.4months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3months (95% CI 0.1 to 12.5months) and DCR of 86.7%. Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.

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 &lt; 0.001) and had fewer comorbidities (e.g. myocardial infarction was associated with reduced probability of receiving either TAS or Rego (p &lt; 0.05)). More were enrolled in preferred provider organization in pts using these agents (45% vs. 37.5%, p &lt; 0.001). In the multivariate analysis, Asian pts had a higher likelihood of using late-line therapies (OR = 1.53, p &lt; 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 &lt; 0.001), had fewer comorbidities, and enrolled in preferred provider organization (47.5% vs. 38.5%, p &lt; 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.

Real-world treatment patterns, healthcare resource utilization and costs of care among newly-diagnosed patients with HR+/HER2- metastatic breast cancer.

1073 Background: Current literature on the treatment patterns and economic burden among newly diagnosed patients (pts) with HR+/HER2- metastatic breast cancer (mBC) is outdated and may not adequately capture the rapidly evolving treatment landscape. This study addresses this gap by providing a contemporary and comprehensive summary of real-world treatment patterns, healthcare resource utilization (HRU) and cost of care among HR+/HER2- mBC pts, through their first 3 lines of treatment (LOT) following metastatic diagnosis (met dx). Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2- mBC between 10/01/2016 - 06/30/2022 from the IQVIA PharMetrics Plus database. Pts were required to have≥ 6 months of follow up post met dx. The study classified pts hierarchically into mutually exclusive treatment categories across 3 LOTs following met dx: endocrine therapy only (ET), CDK4/6 inhibitor-based therapy (CDKi), alpelisib-based therapy (ALP), mTOR inhibitor-based therapy (mTOR), PARP inhibitor (PARPi), or chemotherapy (CT). Categories with &lt; 30 pts in each line or those with overlapping targeted treatments were grouped into “Others'' (OTH). Baseline characteristics were assessed in the 12 months prior to met dx. HRU and costs of care (in 2022 USD) were measured during the follow-up period and reported in per patient per month (PPPM). Results: The study included 2,449 pts, with 64.6%, 10.5%, 22.8%, 2.1% pts receiving CDKi, CT, ET and OTH in 1LOT, respectively. In 2LOT (n=1,164), 41% of pts received CDKi, 24% CT, 20% ET, 9% mTOR, 4% ALP and 3% OTH. In 3LOT (n=479), 44% of pts received CT, 21% CDKi, 15% ET, 9% mTOR, 6% ALP and 4% OTH. The median treatment duration in 1LOT was longest for pts receiving CDKi (23.5 months) compared to 17.1 months for ET. The PPPM total costs were $15,396, $16,955 and $17,853 in 1, 2 and 3LOT. In 1LOT, CDKi pts had the highest PPPM costs [Table]. In the 2/3 LOT, ALP-treated pts incurred the highest costs followed by CDKi in 2LOT and mTOR-treated pts in 3LOT (Table). CT and ALP had the highest ER visits in 2 (0.18 and 0.13) and 3 LOT (0.20 and 0.27). Conclusions: The majority of patients received CDKi treatment as their 1LOT with a more fragmented treatment landscape in the 2/3LOTs. The incorporation of agents targeting the PI3K pathway (ALP and mTOR) remained low in the 2/3LOTs. Costs associated with the same targeted treatment increased when used in later lines of therapy. Early optimization of targeted therapy and a focus on adverse event management may be associated with economic benefits. [Table: see text]

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment.

Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.

Genomic alterations (GA) in ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) patients (pts) with metastatic breast cancer (MBC): Co-occurrence and prevalence along treatment course.

1060 Background: The standard of care for HR(+) HER2(-) MBC is evolving with new biomarker-guided drugs, including novel selective estrogen receptor degraders (SERDs) for pts with ESR1 mutations (mut) and PIK3CA and AKT inhibitors for pts with alterations in the PI3K pathway (PIK3CA, AKT1, and PTEN). This study aimed to evaluate the co-occurrence and the prevalence of these GA in different metastatic lines of therapy in real-world practice for MBC. Methods: This study included pts with HR(+) HER2(-) MBC who underwent genomic testing using Foundation Medicine tissue or liquid comprehensive genomic profiling assays, with specimens collected within 60 days of therapy initiation. Clinical data were obtained by the nationwide (US-based) de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast cancer database (FH-FMI CGDB), originated from ~280 US cancer clinics (~800 sites of care) between 01/2011-06/2023. The prevalence of ESR1mut, PIK3CAmut, AKT1, PTENmut, and PTEN copy loss were calculated in tissue (TBx) and liquid biopsies (LBx) collected at time of 1st, 2nd, and 3rd lines of therapy. The co-occurrence of GA in TBx was evaluated. Results: Among patients with a TBx collected around therapy initiation (n=2,536), 81.5% (2,066) was collected at 1st, 10.2% (258) at 2nd, and 8.3% (212) at 3rd line. Among patients with a LBx collected around therapy initiation (n=545), 47% (256) was collected at 1st, 33.2% (181) at 2nd, and 19.8% (108) at 3rd line. In TBx, the prevalence of GA detected in 1st, 2nd, and 3rd lines were 58.6% (1,210), 67.4% (174), and 71.2% (151), respectively. In LBx, the prevalence was 42.7% (121), 65.7% (119), and 60.1% (65), respectively. Among LBx with tumor fraction ³1%, the prevalence was 67.9% (74/109), 89.1% (81/91), and 84.3% (43/51). Among patients with a GA detected in TBx 1st (n=1,210), 2nd (n=174), and 3rd (n=151) lines, both ESR1mut and a PIK3 pathway GA was detected in 7.4% (90), 12.1% (21), and 23.8% (36), respectively. Conclusions: In our dataset, 42-59% of patients with HR(+) HER2(-) MBC have at least one GA detected by TBx or LBx in 1st line, with prevalence increasing in later lines of therapy to 60-71% due to acquisition of an ESR1mut. PTEN copy loss is detected at much higher rates in TBx than LBx, consistent with the known inherent limitations of ctDNA testing. Serial genomic testing with LBx with reflex TBx if alterations are not identified should strongly be considered with the recent approvals of several molecularly targeted agents for HR(+) HER2(-) MBC. [Table: see text]

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Stereotactic body radiation therapy combined with atezolizumab and bevacizumab for hepatocellular carcinoma with extrahepatic metastasis: Preliminary result of a single-arm study.

e16205 Background: IMbrave150 study confirmed the clinical benefit of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma (HCC). However, patients with extrahepatic metastasis (EHS) had a poorer prognosis. Studies suggested “abscopal effect” of synchronous radiotherapy and immunotherapy may improve antitumor activity. This study aimed to evaluate efficacy and safety of stereotactic body radiation therapy (SBRT) combined with atezolizumab and bevacizumab in HCC patients with EHS. Methods: This single-arm study included HCC patients with EHS from January 2022 to November 2023 in Fudan University Shanghai Cancer Center. Prior tyrosine kinase inhibitor and/or immune checkpoint inhibitor treatment were eligible. After first dose atezolizumab and bevacizumab, SBRT was performed with a total dose of 25-50 Gy. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS), disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), and duration of response (DOR). Results: Thirty-nine patients were included. Fourteen patients were treated as first-line therapy and 25 patients were treated as later-line therapy. The mean age was 56.69±11.21 years and 89.7% were male. Of these patients, 66.7% had hepatitis viral infection and 25.6% had vascular invasion. 53.8% of patients had ≥2 extrahepatic spread lesions. In addition, 33.3% of patients had received prior immunotherapy and 23.1% of patients had received tyrosine kinase inhibitor therapy. The median follow-up was 6.50 (range: 1.43-22.17) months. The ORR and DCR were 43.6% and 92.3%, respectively. The ORR was 57.1% and 36.0% in first-line subgroup and later-line subgroup, respectively. The 12-month OS rates was 54.7%. The median PFS, median TTP and median DOR were 6.73 months, 8.67 months, and 7.17 months, respectively. The incidence of all grade TRAE and grade ≥3 TRAE were 38.5% and 12.8%, respectively. The most common grade ≥3 TRAEs were decreased platelet count (7.7%), decreased white blood cell count (2.6%), pruritus (2.6%) and rectal bleeding (2.6%). No serious adverse events occurred. Conclusions: SBRT combined with systemic atezolizumab and bevacizumab showed encouraging efficacy with manageable safety profile for HCC patients with EHS regardless of prior treatment. Further studies are warranted. Clinical trial information: NCT05396937 . [Table: see text]

A multi-center retrospective study on the efficacy and safety of regorafenib plus immune checkpoint inhibitors with or without TACE as a second-line treatment for advanced hepatocellular carcinoma.

e16147 Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the efficacy and safety of regorafenib plus immune checkpoint inhibitors (ICIs) with transarterial chemoem bolization (R+ICIs+TACE) versus regorafenib plus ICIs (R+ICIs) as a second-line treatment for patients with advanced HCC. Methods: This retrospective study included patients with advanced HCC from our multicenter who received R+ICIs+TACE or R+ICIs as a later-line therapy from June 2020 to August 2022.Objective response rate (ORR), disease control rate (DCR), median progression-free survival (m-PFS), and safety were evaluated according to the modified Response Evaluation Criteria in Solid Tumors(m-RECIST). Factors affecting PFS and OS were analyzed using a Cox proportional-hazards regression model. Results: A total of 78 patients were included in the study (regardless of first-line treatment), including 48 who received R+ICIs+TACE and 30 who received R+ICIs. The R+ICIs+TACE group had a significantly higher ORR (31.6% vs. 9.8%, P = 0.021), higher DCR (73.8%vs. 45.7%, P = 0.008), longer PFS (median 8.5 vs.3.6 months, P &lt; 0.0001) and and a longer OS (14.6 vs 8.5 months, P = 0.024) than those who received R+ICIs group. Child-Pugh class A6 and B7, R+ICIs and extrahepatic metastasis were found as independent prognostic factors for poor PFS. R+ICIs, a-fetoprotein &gt; 400 ng/mL and Child-Pugh class were noted as independent prognostic factors for poor OS.There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (76.8% vs. 71.3%, P = 0.41) and the incidence of grade 3/4 serious adverse effects (6.2% vs. 16.1%, P = 0.21) between the two group. Conclusions: Regorafenib plus ICIs with TACE showed a promising efficacy with favorable safety in HCC patients with PD-1 inhibitor resistance, especially in the standard second line patients.