1295P Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFR mutated (EGFRm) advanced NSCLC: FLAURA China study overall survival (OS)

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.

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P1.01-112 Osimertinib vs Standard of Care (SoC) EGFR-TKI as First-Line Treatment in Chinese Patients With EGFRm Advanced NSCLC

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.669 ◽

2018 ◽

Vol 13 (10) ◽

pp. S507-S508

Author(s):

C. Zhou ◽

Y. Cheng ◽

Y. He ◽

W. Li ◽

H. Zhang ◽

...

Keyword(s):

Advanced Nsclc ◽

Standard Of Care ◽

Chinese Patients ◽

Line Treatment ◽

First Line ◽

Egfr Tki ◽

First Line Treatment

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Economic Analysis of First-Line Treatment with Erlotinib in an EGFR -Mutated Population with Advanced NSCLC

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2016.02.004 ◽

2016 ◽

Vol 11 (6) ◽

pp. 801-807 ◽

Cited By ~ 13

Author(s):

Alain Vergnenegre ◽

Bartomeu Massuti ◽

Filippo de Marinis ◽

Enric Carcereny ◽

Enriqueta Felip ◽

...

Keyword(s):

Economic Analysis ◽

Advanced Nsclc ◽

Line Treatment ◽

First Line ◽

Egfr Mutated ◽

First Line Treatment

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First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Oncology ◽

10.3389/fonc.2021.598265 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiang Wu ◽

Wuxia Luo ◽

Wen Li ◽

Ting Wang ◽

Lin Huang ◽

...

Keyword(s):

First Generation ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Meta Analysis ◽

Controlled Trials ◽

Line Treatment ◽

First Line ◽

Randomized Controlled ◽

Egfr Tki ◽

First Line Treatment

ObjectiveThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.MethodsA systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.ResultsA total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50–0.64; P <0.00001) and 0.70 (95% CI = 0.54–0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.ConclusionsCompared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.

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First-generation EGFR-TKI plus chemotherapy versus EGFR-TKI alone as first-line treatment in advanced NSCLC with EGFR activating mutation: a systematic review and meta-analysis of randomized controlled trials

10.1101/2020.04.17.046409 ◽

2020 ◽

Author(s):

Qiang Wu ◽

Wuxia Luo ◽

Wen Li ◽

Ting Wang ◽

Lin Huang ◽

...

Keyword(s):

First Generation ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Meta Analysis ◽

Controlled Trials ◽

Line Treatment ◽

First Line ◽

Randomized Controlled ◽

Egfr Tki ◽

First Line Treatment

AbstractThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation. A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI=0.50-0.64; P < 0.00001) and 0.70 (95% CI=0.54-0.90; P=0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P=0.02) and concurrent therapy (P=0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia. In conclusion, compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC, yet at the price of increasing incidence of chemotherapy-induced toxicities that is well tolerated and clinically manageable.

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151P Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for advanced NSCLC with EGFR-positive mutation patients: A systematic review

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(21)01993-6 ◽

2021 ◽

Vol 16 (4) ◽

pp. S779-S780

Author(s):

S. Chen ◽

E. Marcella ◽

B. Susanto ◽

J. Tandiono ◽

R.S. Heriyanto ◽

...

Keyword(s):

Systematic Review ◽

Advanced Nsclc ◽

Standard Of Care ◽

Line Treatment ◽

First Line ◽

Egfr Tki ◽

First Line Treatment

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Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7521 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7521-7521 ◽

Cited By ~ 47

Author(s):

Tetsuya Mitsudomi ◽

Satoshi Morita ◽

Yasushi Yatabe ◽

Shunichi Negoro ◽

Isamu Okamoto ◽

...

Keyword(s):

Overall Survival ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Significant Difference ◽

The Impact ◽

Egfr Tki ◽

First Line Treatment ◽

Platinum Doublet

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.

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