First-Line Advanced Research Articles

S1469 Understanding Gastroenterologist Preferences at the Time of Treatment Escalation to First-Line Advanced Therapies in Ulcerative Colitis: A Discrete Choice Experiment in Five European Countries

S1469 Understanding Gastroenterologist Preferences at the Time of Treatment Escalation to First-Line Advanced Therapies in Ulcerative Colitis: A Discrete Choice Experiment in Five European Countries

S1049 Real World Comparison of Effectiveness, Durability, and Safety of First-Line Advanced Therapies for Ulcerative Proctitis

S1049 Real World Comparison of Effectiveness, Durability, and Safety of First-Line Advanced Therapies for Ulcerative Proctitis

Real-World Comparison of Effectiveness, Treatment Persistence, and Safety of First-Line Advanced Therapies at 1 Year for Ulcerative Proctitis

Lay Summary In this retrospective cohort study, vedolizumab was associated with higher odds of steroid-free clinical remission at 1 year compared to anti-TNF agents for bio-naïve patients with ulcerative proctitis.

PP01.85 A Phase 2/3 Study of Fianlimab, Cemiplimab, plus Chemotherapy Versus Cemiplimab plus Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer

PP01.85 A Phase 2/3 Study of Fianlimab, Cemiplimab, plus Chemotherapy Versus Cemiplimab plus Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer

Cost-Effectiveness of Vedolizumab as a First-Line Advanced Therapy Versus Adalimumab Treatment Sequences for Ulcerative Colitis in Italy.

Today, there are many treatment options available for the management of ulcerative colitis, creating challenges in selecting the most efficacious and cost-effective treatment sequences. Treatments in the anti-tumor necrosis factor alpha (TNFα) therapeutic class, as well as vedolizumab, are widely used and endorsed as first-line options according to treatment guidelines. The aim of this study was to compare treatment sequences involving vedolizumab and the anti-TNFα treatment adalimumab in terms of cost-effectiveness in the treatment of moderately to severely active ulcerative colitis in Italy. A cost-effectiveness model comparing treatment sequences within the Italian National Health Service in terms of costs and quality-adjusted life years (QALYs) with a lifetime horizon was developed. The analysis focused on the relative positioning of vedolizumab and adalimumab, leveraging the results of the landmark head-to-head VARSITY clinical trial as key inputs. The robustness of the results was investigated through a range of sensitivity and scenario analyses. The strategy of vedolizumab as a first-line advanced therapy followed by adalimumab was associated with higher costs and health benefits compared with first-line adalimumab followed by vedolizumab. The incremental cost-effectiveness ratio was €16,146/QALY, which was found to be robust to changes to inputs associated with areas of high uncertainty. This economic evaluation estimated a 94% probability that vedolizumab as a first-line advanced therapy is cost-effective at a threshold of €33,004/QALY when compared with first-line adalimumab sequences. Using clinical trial evidence to inform the efficacy of second-line treatments estimated that the effectiveness of anti-TNFα treatments is not substantially reduced by vedolizumab exposure.

Use of Different Anti-PD-1 Checkpoint Combination Strategies for First-Line Advanced NSCLC Treatment-The Experience of Ion Chiricuță Oncology Institute.

Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0-1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials.

Association Between Intermediate End Points, Progression-free Survival, and Overall Survival in First-line Advanced or Recurrent Endometrial Cancer

PurposeAdvanced/recurrent endometrial cancer is associated with poor long-term outcomes. Clinical studies of novel regimens are ongoing, but given that data on overall survival (OS) take a long time to mature, surrogate end points are often used to support clinical-research interpretation. The aim of this study was to explore the correlation between progression-free survival (PFS)/time to progression (TTP) and OS across multiple time points in the first-line treatment of advanced/recurrent endometrial cancer. MethodsThis study comprised meta-analyses of Phase 2/3 randomized, controlled trials of first-line treatments in patients with advanced primary or first-recurrent endometrial cancer identified via systematic literature review. The strength of the surrogacy relationship was assessed by correlation analyses (estimated with Spearman and Pearson correlation coefficients) and weighted linear regression. FindingsData from 15 studies were included. PFS and TTP (TTP was reported in one study only) were highly correlated with future OS at multiple time points (Spearman values, 0.83–0.90; Pearson values, 0.86–0.93), suggesting that a change in PFS/TTP would likely be correlated with a change in OS in the same direction. On weighted linear regression, a 10% increase in PFS/TTP probability was significantly associated with a 9.3% to 13.3% increase in the probability of future OS. The strong positive association between PFS/TTP and OS was supported by findings from sensitivity analyses based on identified sources of interstudy heterogeneity. ImplicationsPFS/TTP is a good potential candidate for predicting long-term OS outcomes in trials of first-line treatment in patients with advanced/recurrent endometrial cancer. The findings from this report may help to inform health-authority and clinical decision makers that PFS/TTP improvements are likely to translate into subsequent OS improvements once data mature.

MSR29 Application of Bayesian Multi-Parameter Evidence Synthesis to Achieve Clinical Plausibility of Lifetime Survival Extrapolations in First-Line Advanced Non-Small Cell Lung Cancer (aNSCLC)

Lifetime overall survival (OS) extrapolations are required to estimate important differences in costs and benefits between comparators in health economic models. Bayesian multi-parameter evidence synthesis (B-MPES) models for aNSCLC patients receiving second-line nivolumab have previously demonstrated clinically reasonable and stable estimates for long-term OS. Here, we investigate the plausibility of B-MPES predictions for OS in the CheckMate 227 Part 1 trial of nivolumab plus ipilimumab (NIVO+IPI) in aNSCLC patients in the first-line setting and compare with uninformed standard parametric models (SPMs).

A Comparison of Alternative Network Meta-Analysis Methods in the Presence of Nonproportional Hazards: A Case Study in First-Line Advanced or Metastatic Renal Cell Carcinoma

ObjectivesNetwork meta-analysis (NMA) of time-to-event outcomes based on constant hazard ratios can result in biased findings when the proportional hazards (PHs) assumption does not hold in a subset of trials. We aimed to summarize the published non-PH NMA methods for time-to-event outcomes, demonstrate their application, and compare their results. MethodsThe following non-PH NMA methods were compared through an illustrative case study in oncology of 4 randomized controlled trials in terms of progression-free survival and overall survival: (1) 1-step or (2) 2-step multivariate NMAs based on traditional survival distributions or fractional polynomials, (3) NMAs with restricted cubic splines for baseline hazard, and (4) restricted mean survival NMA. ResultsFor progression-free survival, the PH assumption did not hold across trials and non-PH NMA methods better reflected the relative treatment effects over time. The most flexible models (fractional polynomials and restricted cubic splines) fit better to the data than the other approaches. Estimated hazard ratios obtained with different non-PH NMA methods were similar at 5 years of follow-up but differed thereafter in the extrapolations. Although there was no strong evidence of PH violation for overall survival, non-PH NMA methods captured this uncertainty in the relative treatment effects over time. ConclusionsWhen the PH assumption is questionable in a subset of the randomized controlled trials, we recommend assessing alternative non-PH NMA methods to estimate relative treatment effects for time-to-event outcomes. We propose a transparent and explicit stepwise model selection process considering model fit, external constraints, and clinical validity. Given inherent uncertainty, sensitivity analyses are suggested.

EE466 Budget Impact Analysis of Cemiplimab for First-Line (1L) Advanced Non-Small Cell Lung Cancer (NSCLC) With Programmed Cell Death-Ligand 1 (PD-L1)≥ 50% in Italy

EE466 Budget Impact Analysis of Cemiplimab for First-Line (1L) Advanced Non-Small Cell Lung Cancer (NSCLC) With Programmed Cell Death-Ligand 1 (PD-L1)≥ 50% in Italy

Interest of the Addition of Taxanes to Standard Treatment in First-Line Advanced HER2 Positive Gastroesophageal Adenocarcinoma in Selective Patients.

BackgroundStudies have reported a beneficial role of the addition of trastuzumab to platin-5-FU based chemotherapy in first-line advanced HER2 positive gastroesophageal adenocarcinoma (GEA). However, the effect of taxanes combined with platin-5FU + trastuzumab (PFT) is understudied.MethodsWe performed a retrospective cohort study to evaluate the interest of taxanes among HER2-positive advanced GEA patients treated with PFT. We enrolled HER2-positive advanced GEA patients who underwent treatment between January 2009 to March 2021 in seven hospitals centers in France, treated with PFT alone (S group) or with taxanes + PFT regimen (T group). The primary outcome was progression-free survival (PFS). Also, overall survival (OS), response rate, conversion surgery rate, and safety were evaluated.ResultsOverall, 65 patients received PFT-based therapy, 24 patients in the T group, and 41 patients in the S group. To avoid the selection bias, only those patients presenting an ECOG-PS of 0-1 and synchronous metastasis (21 patients in the T group and 19 patients in the S group) were included for analysis. The median PFS was 9.3 months (95%CI 7.0 to 17.2) in the T group and 5.9 months (95%CI 3.7 to 9.6) in the S group (log-rank p=0.038). Treatment by taxanes was significantly associated with a better PFS in univariate (HR 0.49; 95%CI 0.25 to 0.98, p=0.042) and multivariate Cox regression analysis (HR 0.44; 95%CI 0.21 to 0.94, p=0.033), and IPTW method (HR 0.56; 95% CI 0.34 to 0.91, p=0.019). OS was prolonged (19.0 months (95%CI 7.8 to 45.2) vs 13.0 months (95%CI 5.5 to 14.8), log-rank p=0.033) in favor of the T group. Treatment by taxanes was significantly associated with a better OS in univariate Cox regression analysis (HR 0.49; 95%CI 0.21 to 0.96, p=0.038) and IPTW method (HR 0.49; 95% CI 0.29 to 0.84, p=0.009). The response rate was higher in the T group, with conversion surgery in five patients. No treatment-related death was observed in both groups.ConclusionsGiven the improvement in PFS and OS, the addition of taxanes to standard chemotherapy could be considered as a promising treatment for selected HER2-positive advanced GEA patients, with PS 0-1 and synchronous metastasis (NCT04920747).

Clinical Controversies in Psoriatic Disease: The Use of IL-17i/IL-23i Versus TNFi as First-line Advanced Therapy in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a complex, heterogeneous disease, with disease activity in various domains. In recent years, many novel treatments with diverse mechanisms of action have been introduced into the clinical setting. Numerous factors go into the choice and sequencing of different therapies for individual patients. At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a point/counterpoint debate was held addressing therapeutic choices. Specifically, the question addressed was whether interleukin (IL)-17/IL-23 inhibitors or tumor necrosis factor inhibitors are the appropriate initial therapy for patients with PsA.

POSA7 Clinical and Health-Related Quality of Life (HRQOL) Outcomes from Interventional Studies in First-Line (1L) Advanced or Metastatic Urothelial Cancer (MUC): A Systematic Literature Review (SLR)

POSA7 Clinical and Health-Related Quality of Life (HRQOL) Outcomes from Interventional Studies in First-Line (1L) Advanced or Metastatic Urothelial Cancer (MUC): A Systematic Literature Review (SLR)

POSA25 An Incremental Effectiveness Analysis of Avelumab in Combination With Axitinib for the Treatment of First-Line Advanced Renal Cell Carcinoma in Portugal

To evaluate the incremental life-years (LY) and quality-adjusted life years (QALY) of avelumab in combination with axitinib compared with sunitinib and pazopanib in the first-line treatment of advanced renal cell carcinoma (aRCC) in patients with intermediate or poor risk and of temsirolimus in patients with poor risk in Portugal.

Biomarkers of Pembrolizumab Efficacy in First-Line Advanced PD-L1 ?50% Non-Small Cell Lung Cancer Treatment

In non-small-cell lung cancers (NSCLC) with programmed death-ligand 1 (PD-L1) expression on ? 50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy.

First-line Advanced Cutaneous Melanoma Treatments: Where Do We Stand?

Cutaneous melanoma has always been a dreaded diagnosis because of its high mortality rate and its proclivity for invasiveness and metastasis. Historically, advanced melanoma treatment has been limited to chemotherapy and nonspecific immunotherapy agents that display poor curative potential and high toxicity. However, during the last decade, the evolving understanding of the mutational burden of melanoma and immune system evasion mechanisms has led to the development of targeted therapy and specific immunotherapy agents that have transformed the landscape of advanced melanoma treatment. Despite the considerable strides in understanding the clinical implications of these agents, there is a scarcity of randomized clinical trials that directly compare the efficacy of the aforementioned agents; hence, there are no clear preferences among the available first-line options. In addition, the introduction of these agents was associated with a variety of dermatologic adverse events, some of which have shown a detrimental effect on the continuity of treatment. This holds especially true in light of the current fragmentation of care provided by the managing health care professionals. In this study, we attempt to summarize the current understanding of first-line treatments. In addition, the paper describes the indirect comparative evidence that aids in bridging the gap in the literature. Furthermore, this paper sheds light on the impact of the scarcity of dermatology specialist input in the management of dermatologic adverse events associated with advanced melanoma treatment. It also looks into the potential avenues where dermatologic input can bridge the gap in the care provided by oncologists, thus standardizing the care provided to patients with melanoma presenting with dermatologic adverse events.

S740 Rates of Treatment Failure Among Patients With Ulcerative Colitis Treated With First-Line Advanced Therapies

S740 Rates of Treatment Failure Among Patients With Ulcerative Colitis Treated With First-Line Advanced Therapies

MO01.06 Real-World Outcomes of Immunotherapy-Based Regimens in First-Line Advanced Non-Small Cell Lung Cancer

MO01.06 Real-World Outcomes of Immunotherapy-Based Regimens in First-Line Advanced Non-Small Cell Lung Cancer

PCN275 Network Meta-Analysis Design Considerations in a Complex and Rapidly Evolving Landscape: A Case Study in First-LINE (1L) Advanced NON-SMALL Cell LUNG Cancer (ANSCLC)

In 1L aNSCLC, the therapeutic landscape is complex and rapidly evolving. While the introduction of different immunotherapy-based treatments reflects advances in treatment efficacy and a shift toward more personalized medicine, it poses challenges in generating unbiased relative effect estimates via network meta-analysis (NMA). Our objective was to illustrate NMA design considerations in the 1L aNSCLC setting. A comprehensive set of NMA checklists was used for presenting NMA design choices in 1L aNSCLC. Using a systematically identified evidence base of 125 randomized controlled trials (RCTs), the following were identified as key design features: 1) proportional hazards assumption violations and differing lengths of follow-up; 2) effect modification, 3) lumping vs. splitting treatment nodes, and 4) study design heterogeneity including differences in blinding, chemotherapy arms, cross-over, and use of subsequent therapies. Methodological approaches to address the identified features were presented. Proportional hazards violations and differing lengths of follow-up were evident in RCTs comparing immunotherapies against chemotherapies. Several approaches were considered, including: constant hazard ratios for trials of similar follow-up; fractional polynomial/parametric NMAs; piecewise hazard ratios; restricted mean survival time; and survival at pre-defined times. Programmed death-ligand 1 expression level and histology were key effect modifying factors for some but not all comparisons in the network. Meta-regression was considered but was infeasible; instead, stratified networks were constructed. The choice to lump/split treatment nodes was endpoint-specific, with some chemotherapy combinations showing similar efficacy yet different safety profiles. Nine RCTs involved investigator’s choice control arms, adding complexity to defining treatment nodes. The cross-over design and use of subsequent therapy evolved over time and was evaluated alongside design heterogeneity using a study-by-study assessment of the potential impact on treatment effect size. We identified and presented approaches for handling multiple NMA design issues in 1L aNSCLC. These issues can be extrapolated and applied to other therapeutic settings.

P070 Patient Perspective and Timing of First-Line Advanced Systemic Treatments in IBD: Results From a National Chart Audit

BACKGROUND: There is increased evidence that early and aggressive use of advanced systemic agents for patients with inflammatory bowel disease (IBD) produces better patient outcomes, particularly for patients afflicted with Crohn’s disease. However, convincing IBD patients to initiate advanced treatment early on can sometimes be difficult. This research sought to better understand the process of beginning first line biologic or JAK treatment and uncover insights into the timing of initiation via assessment of the level of patient engagement, initiation discussion timelines, and general patient attitudes regarding initiation of first line systemic treatment with either a biologic or JAK inhibitor. METHODS: An independent market analytics firm collaborated with US gastroenterologists (n = 219) to conduct a retrospective chart review of patients with either ulcerative colitis (UC) or Crohn’s disease (CD) (n = 1,006), who had been initiated on their first biologic or JAK in the twelve weeks prior to data collection. Gastroenterologists were required to submit at least three and up to seven IBD patient charts. Data were collected in May and June of 2019 and included clinical and non-clinical patient demographics, first-line treatment regimens, reasons for first line brand choice, as well as metrics regarding the treating physician’s perceptions. RESULTS: Collaborating gastroenterologists estimate that 22% of their UC and 24% of their CD patients on first line biologic or JAK therapy should have initiated treatment earlier in their disease. Patients are rarely the individual starting treatment conversations regarding beginning advanced systemic therapy, as physicians report they themselves are the one to initiate this discussion 88% of the time. Among audited IBD patients, treating gastroenterologists report that they had discussed advanced systemic treatment with their patients for an average of 4.7 months prior to beginning therapy with a biologic or tofacitinib. Furthermore, while most patients (63%) had positive emotions about beginning biologic or JAK therapy (excitement or relief), 15% were reportedly resigned to the fact that it was necessary and an additional 22% were anxious about starting treatment. Patients started on tofacitinib first-line were significantly more likely to feel “excited” about beginning treatment than patients initiated on a first line biologic. CONCLUSION(S): With increased evidence of the success of early and aggressive use of biologics or JAKs for the treatment of IBD, it is important for gastroenterologists to begin having discussions with their patients at the first sign of necessity. On average, patients are not initiated on their first biologic or JAK treatment for over four months after physicians first propose the treatment options to their patients. Furthermore, physicians assess that over one in five of their first line biologic or JAK treated patients should have begun treatment earlier in their disease and a similar percent are reportedly “anxious” about starting advanced systemic therapy.