Efficacy of EGFR TKI Targeted Therapy versus TKI in Combination with Chemotherapy in Non-Small-Cell Lung Cancer

Background and Hypothesis: Non-Small Cell Lung Cancer (NSCLC) constitutes the largest proportion of lung cancers and is the foremost cause of mortality associated with cancer around the world. Of patients with non-small cell lung cancer, approximately 15% of Caucasians and 30% of Asians have activating mutations in the epidermal growth factor receptor (EGFR) gene. Numerous studies have indicated increased progression free survival after treatment with tyrosine kinase inhibitors (TKI). However, the most efficacious combination of drugs, whether TKIs, chemotherapy, or anti-angiogenesis, is still unknown. This literature review will be constructed to determine whether tyrosine kinase inhibitor targeted therapy in combination with chemotherapy or anti-angiogenesis drugs is more effective in prolonging progression free survival in EGFR-mutated NSCLC as opposed to tyrosine kinase inhibitor targeted therapy alone. Project Methods: The methodology of this proposed literature review is an online search of PubMed, Journal of Clinical Oncology, and important scientific conferences. The treatment interventions consist of tyrosine kinase inhibitor targeted therapy in combination with chemotherapy and tyrosine kinase inhibitor targeted therapy alone. The projected outcome is an increase in progression free survival and overall survival. The proposed data analysis consists of constructing a forest plot in order to display the results. Results: The results are expected to support the hypothesis, that combination treatment with TKI and chemotherapy will allow patients with an opportunity to prolong their progression-free survival. The forest plot is expected to indicate a progression-free survival hazard ratio that favors combination therapy. P-values will be included to indicate statistically significant results. Conclusion and Potential Impact: The importance of finding the answer to this hypothesis is that it will improve treatment outcomes for patients with NSCLC. It will provide patients with a strong alternative to chemotherapy or tyrosine kinase inhibitor therapy alone. Most importantly, it will provide patients with an avenue to increase their progression-free survival.

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First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9508 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9508-9508 ◽

Cited By ~ 7

Author(s):

Xiaoshan Wang ◽

Ming Zeng

Keyword(s):

Overall Survival ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Tyrosine Kinase Inhibitor ◽

Stereotactic Radiotherapy ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival

9508 Background: The effectiveness of aggressive local therapy for oligometastatic non-small-cell lung cancer (NSCLC) is unknown. This multi-institutional, randomized, open label, phase III clinical trial was performed to assess upfront stereotactic radiotherapy to all sites at diagnoses in previously untreated EGFRm oligometastatic non-small-cell lung cancer on progression-free survival and overall survival. Methods: The study was conducted at five centers located in different provinces of China.Eligible participants had pathologically confirmed adenocarcinoma, gene sequencing confirmed EGFRm, stage IV, five or fewer metastatic disease lesions, an ECOG performance status score of ≤ 2, systemic therapy naive, and no brain disease before randomization.Participants were randomized to receive either first-line tyrosine kinase inhibitor (TKI) treatment alone or up front stereotactic radiotherapy to all sites of disease along with TKI treatment.The primary endpoint was progression-free survival and the secondary endpoint was overall survival. Results: From January 2016 to January 2019, 133 participants were enrolled, including 65 (48.8%) in the TKI arm who received standard of care TKI alone and 68 (51.1%) in the stereotactic radiotherapy sites at diagnosis arm who received stereotactic radiotherapy and TKI.At a median follow-up of 19.6 months (IQR 9.4 - 41.0), the median progression-free survival for tyrosine kinase inhibitor alone was 12.5 months, and for tyrosine kinase inhibitor and stereotactic radiotherapy was 20.20months, respectively (HR 0.6188 [95% CI 0.3949-0.9697], log rank P< .001). The median overall survival in the TKI alone arm was 17.40 months, and for TKI and stereotactic radiotherapy arm was 25.50 months, respectively (HR 0.6824 [95% CI 0. 4654-1.001], log rank P< .001). Adverse events were similar between groups, with no grade 5 or deaths due to treatment. Grade 3/4 adverse events with or without radiotherapy included pneumonitis (7.3% vs. 2.9%; P> .05) and esophagitis (4.4%vs. 3.0% P> .05). Conclusions: Upfront stereotactic radiotherapy to sites at diagnosis along with first line TKI improved both progression-free survival and overall survival significantly compared with TKI alone. This finding suggests aggressive local therapy to sites at diagnosis should be explored further in large cohort phase III trials as a standard treatment option in this clinical scenario. Clinical trial information: NCT02893332 .

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Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA

Future Oncology ◽

10.2217/fon-2021-0549 ◽

2021 ◽

Author(s):

Masahiro Tsuboi ◽

Walter Weder ◽

Carles Escriu ◽

Collin Blakely ◽

Jianxing He ◽

...

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Tyrosine Kinase Inhibitor ◽

Cell Lung Cancer ◽

Kinase Inhibitor ◽

Small Cell ◽

Small Cell Lung ◽

Egfr Tyrosine Kinase Inhibitor ◽

Free Survival

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II–IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov)

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