scholarly journals Optimizing therapy sequence to prevent patient attrition in EGFR mutation-positive advanced or metastatic NSCLC

2020 ◽  
Author(s):  
Julia Roeper ◽  
Sylke Kurz ◽  
Christian Grohé ◽  
Frank Griesinger

Clinical trial and real-world data in non-small-cell lung cancer indicate that 10–60% of patients that progressed on first- or second-generation EGFR-targeting tyrosine kinase inhibitors (TKI) do not receive systemic second-line therapy. In our article, we discuss efficacy, safety and treatment duration with different EGFR-TKIs and stress the need for delivery of the most efficacious therapy in the first-line. We also provide our perspective on analysis of circulating tumor DNA and the role of EGFR-TKI in combined therapies. Finally, we review new therapeutic options to overcome resistance to EGFR-TKI. We believe that overall treatment duration and access to different medications in subsequent lines of therapy should be considered when planning the optimal treatment strategy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 289-289
Author(s):  
Rahul Shenolikar ◽  
Sizhu Liu ◽  
Jenny Tse ◽  
Yao Cao ◽  
Aimee Near

289 Background: Among mNSCLC patients positive for EGFR mutation (EGFRm), first-line (1L) treatment with an EGFR TKI is recommended for best outcomes. This study describes real-world treatment patterns of mNSCLC patients using EGFR TKIs in the 1L setting, including osimertinib, the most recently approved EGFR TKI for 1L use. Methods: Patients with ≥1 claim for an EGFR TKI (1st generation [1G]: gefitinib, erlotinib; 2nd generation [2G]: afatinib, dacomitinib; 3rd generation: osimertinib) from January 1, 2015 – April 30, 2020 were identified in IQVIA’s prescription (LRx) and medical claims (Dx) databases; first date of EGFR TKI was the index date. Patients had 12-month baseline period before index, variable follow-up after index, ≥1 lung cancer diagnosis on index or in baseline, and earliest metastatic cancer diagnosis on or 90 days before index. Kaplan-Meier analysis was used to estimate 1L treatment duration, where treatment discontinuation was defined as >60-day gap in medication supply of the index EGFR TKI. Patient characteristics and treatment patterns were stratified by 1L EGFR TKI. Results: Overall, 2,505 mNSCLC patients received 1L EGFR TKI (982 osimertinib, 1,060 1G, 463 2G). Median ages were 66-69 years, 64.6-67.1% were female, and 32.4-38.9% had central nervous system metastases on or before index. Most patients were commercially insured (50.8-62.9%), 35.3-45.9% had Medicare, and 0.6-3.3% had other payer types. Nearly all patients had 1L EGFR TKI monotherapy (97.6-99.7%). 1L treatment duration was longer for osimertinib compared to 1G or 2G EGFR TKI (median months, 17.8, 8.7, 10.5 respectively). 2L treatment was observed in 32.5% of 1G and 36.3% of 2G EGFR TKI cohorts. Osimertinib monotherapy, chemotherapy, and immunotherapy (monotherapy or combined with chemotherapy) accounted for 58.3%, 7.0%, and 4.3% of 2L treatments after 1L 1G EGFR TKI, respectively, and 60.7%, 4.2%, and 4.8% of 2L treatments after 1L 2G EGFR TKI. Conclusions: In real-world practice, 1L treatment duration is longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs, mainly osimertinib, given its recent approval.


Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 803 ◽  
Author(s):  
Ming-Szu Hung ◽  
Jr-Hau Lung ◽  
Yu-Ching Lin ◽  
Yu-Hung Fang ◽  
Shu-Yi Huang ◽  
...  

Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77–0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0–11.8, vs. 15.0 months, 95% CI 11.7–28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4–37.2, vs. 55.6 months, 95% CI 25.8–61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis.


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