PP229 Surrogate Outcomes In Health Technology Assessments Of Oncology Drugs: The Osimertinib Case

2020 ◽  
Vol 36 (S1) ◽  
pp. 21-22
Author(s):  
Milton Rodriguez-Zuniga ◽  
Paola Rivera-Ramirez ◽  
Fabian Fiestas-Saldarriaga
Keyword(s):  
Decision Making ◽  
Overall Survival ◽  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Advanced Nsclc ◽  
First Line ◽  
Surrogate Outcome ◽  
Surrogate Outcomes ◽  
Egfr Tki ◽  
Egfr T790m

IntroductionDecision making in publicly funded healthcare systems must rely on patient-relevant outcomes that directly measure clinical benefit, such as overall survival and quality of life (QoL). However, studies that support market authorization of oncology drugs usually assess surrogate outcomes, without having previously demonstrated that these intermediate outcomes reliably predict clinical outcomes. As part of an HTA process, we evaluated the clinical benefit of osimertinib, compared with platinum-pemetrexed combination chemotherapy, in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) that has progressed after first-line EGFR tyrosine kinase inhibitor (TKI) therapy.MethodsWe conducted a systematic search of the PubMed database for randomized controlled trials (RCT) published from inception to January 2019. The clinical outcomes of interest were overall survival and QoL. Where trials reported surrogate outcomes, we conducted additional PubMed searches for evidence of validity for predicting clinical outcomes and used guidance on surrogate outcome validation in oncology from the Institute for Quality and Efficiency in Health Care.ResultsEvidence on osimertinib, compared with chemotherapy, for patients with T790M-positive advanced NSCLC that has progressed after EGFR-TKI therapy was obtained from the AURA3 trial. In this study, overall survival data were immature and the results for QoL and symptom domains were not clinically meaningful. In addition, median progression-free survival (PFS) was six months longer for osimertinib than for chemotherapy. However, to date, no study has demonstrated that PFS reliably predicts longer survival or better QoL.ConclusionsOur HTA suggested that, unless proven, PFS should not be used as a valid surrogate outcome for decision making in public health. For example, the results of the AURA3 trial showed that osimertinib has an effect on the surrogate outcome of PFS in patients with EGFR T790M-positive advanced NSCLC that has progressed after first-line EGFR-TKI therapy, but not on the clinically relevant outcomes of overall survival and QoL. Furthermore, currently available evidence has failed to prove that PFS reliably predicts outcomes that are clinically relevant. Despite this, osimertinib has been given marketing authorization and is widely recommended in clinical guidelines.

scholarly journals Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis

2019 ◽  
Vol 30 ◽  
pp. v914-v915 ◽  
Author(s):  
S.S. Ramalingam ◽  
J.E. Gray ◽  
Y. Ohe ◽  
B.C. Cho ◽  
J. Vansteenkiste ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Advanced Nsclc ◽  
Line Treatment ◽  
First Line ◽  
Egfr Tki ◽  
Overall Survival Analysis ◽  
First Line Treatment

FP03.03 ECOG PS of 0-1 and Very High PD-L1 Expression ≥90% Are Associated With Clinical Benefit From First-Line Chemo-Immunotherapy in Advanced NSCLC

2021 ◽  
Vol 16 (10) ◽  
pp. S948-S949
Author(s):  
B. Ricciuti ◽  
J. Alessi ◽  
S. Alden ◽  
G. Recondo ◽  
M. Nishino ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Advanced Nsclc ◽  
First Line ◽  
Ecog Ps ◽  
Very High

scholarly journals Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes

2018 ◽  
Vol 29 ◽  
pp. ix150 ◽  
Author(s):  
D. Planchard ◽  
M. Boyer ◽  
J.-S. Lee ◽  
A. Dechaphunkul ◽  
P. Cheema ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Standard Of Care ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Egfr Tki

Penpulimab in combination with anlotinib as first-line treatment in advanced nonsquamous non-small-cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21072-e21072
Author(s):  
Baohui Han ◽  
Jianhua Chen ◽  
Ziping Wang ◽  
Xingya Li ◽  
Lin WANG ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Advanced Nsclc ◽  
Locally Advanced ◽  
Drug Binding ◽  
Line Treatment ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Metastatic Nsclc ◽  
First Line Treatment

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.

Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 409-409
Author(s):  
Deniz Tural ◽  
Omer Fatih Olmez ◽  
Ahmet Taner Sümbül ◽  
Mehmet Artac ◽  
Nail Ozhan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Benefit ◽  
Progressive Disease ◽  
Univariate Analysis ◽  
First Line ◽  
Exact Test ◽  
Best Response ◽  
Metastatic Urothelial Carcinoma ◽  
Line Chemotherapy

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p <0.001). In addition, Patients with clinical benefit from first-line chemotherapy (HR= 0.39; 95% CI 0.24-0.65; p <0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factor on OS in patients' use of atezolizumab as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

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