EGFR tyrosine kinase inhibitor therapy continuation with high-dose hypofractionated radiotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) patients with oligoprogressive disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21580-e21580
Author(s):  
Mariacarmela Santarpia ◽  
Maria Rosaria Valerio ◽  
Nicolò Borsellino ◽  
Andrea Girlando ◽  
Gianfranco Mancuso ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
First Line ◽  
Egfr Mutant ◽  
Nsclc Patients

e21580 Background: EGFR tyrosine kinase inhibitors (TKIs) represent the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, despite initial marked responses, tumors invariably develop acquired resistance to TKIs. Oligoprogression is commonly observed during treatment with oncogene-directed therapies, including EGFR TKIs, and refers to patients who experience disease progression only in limited sites as a result of heterogeneous mechanisms of resistance. The use of local ablative treatments for these resistant lesions may extend the duration of TKI therapy and potentially improve long-term disease control and survival. We e retrospectively analyzed the efficacy of EGFR TKI therapy continuation with high-dose hypofractionated radiation therapy (RT), in EGFR-mutant NSCLC patients with oligoprogressive disease. Methods: Patients with metastatic EGFR mutant NSCLC who developed oligoprogression during first-line treatment with gefitinib were included in this analysis. We evaluated progression-free survival 1 (PFS 1), defined as the time from initiation of TKI therapy until development of oligoprogression or death, and PFS 2, defined as time of focal progression until further progression of disease or death. Overall survival and safety were also assessed. Results: Thirty-six patients were included in the study. The median PFS 1 was 12.5 (4.0-23.2) months. High-dose hypofractionated RT consisted of intensity-modulated RT in 23 patients (64%) and stereotactic radiotherapy in 13 cases (36%). The median PFS 2 was 6.3 (2-12.5) months. Overall survival was 38.7 months (9.0-46.3). The treatment was well-tolerated and no patient had to discontinue TKI therapy because of adverse events during radiotherapy. Conclusions: Our therapeutic strategy, including high-dose hypofractionated RT in addition to TKI therapy, was feasible in the clinical setting and was associated with significant prolongation of disease control and improvement of survival outcomes, while being associated with manageable side effects. Our study further support the use of definitive therapeutic approaches in oligoprogressive disease, especially in oncogene-driven tumors. Molecular profiling of metastatic sites remains crucial to identify novel biomarkers, involved in the development of acquired resistance and oligoprogression, that may be useful to select patients for local treatments.

Impact of early progression on prognosis for non-small cell lung cancer patients with EGFR mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20570-e20570
Author(s):  
Kanako Yoshitsugu ◽  
Hirotsugu Kenmotsu ◽  
Katsuhiro Omae ◽  
Shota Omori ◽  
Kazuhisa Nakashima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liver Metastasis ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
First Line ◽  
Early Progression ◽  
Egfr Mutant ◽  
Nsclc Patients

e20570 Background: For epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients, EGFR-tyrosine kinase inhibitors (TKIs) improve progression free survival compared with cytotoxic chemotherapy. However, some patients show early progression (EP) in first-line EGFR-TKI treatment, and their prognosis is still unclear. This study aimed to examine the implications of EP for prognosis of EGFR mutant NSCLC patients. Methods: Advanced EGFR mutant NSCLC patients treated with gefitinib (GEF) as first-line between 2005 and 2015 at Shizuoka Cancer Center were retrospectively reviewed. EP on GEF was defined as disease progression before 180 days according to the Jackman criteria. Results: Forty-five of 198 patients treated with GEF as first-line, showed EP. Patient characteristics was as follows (with EP/ without EP) : median age (range), 69 (32-88)/ 70 (35-92) years; male, 40/ 28%; ECOG performance status (PS) 0-1, 64/ 79%; deletion in exon 19 (del 19), 36/ 53%; L858R in exon 21, 53/ 43%; never smoker, 44/ 65%; liver metastasis, 27/ 12%; brain metastasis, 44/ 37%. The median overall survival was 395 days (95% CI: 267-547 days) for patients with EP and 979 days (95% CI: 808-1124 days) for those without EP. Post progression survival after treatment with GEF was significantly shorter in patients with EP (median: 254 days vs. 420 days, HR: 0.55 (95% CI: 0.39-0.79), P < 0.05). Among patients with EP, 56% received subsequent chemotherapy (patients without EP: 71%). In univariate analysis, EP was significantly associated with four factors; liver metastasis, smoking history, PS 2-4, absence of del 19. In multivariate analysis, smoking history (OR: 0.38, 95% CI: 0.18-0.80), PS 2-4 (OR: 0.43, 95% CI: 0.19-0.98), and del 19 (OR: 2.15, 95% CI: 1.04-4.45) were significantly correlated (P < 0.05) with EP. Conclusions: Patients with EP during first-line GEF therapy for advanced EGFR mutant NSCLC showed poor prognosis. Since smokers, patients with PS 2-4, or absence of del 19 tend to show EP, improving first-line treatment is necessary to improve their prognosis.

scholarly journals Afatinib in the first-line treatment of patients with non-small cell lung cancer: clinical evidence and experience

2018 ◽  
Vol 12 ◽  
pp. 175346661880865 ◽  
Author(s):  
Biagio Ricciuti ◽  
Sara Baglivo ◽  
Andrea De Giglio ◽  
Rita Chiari
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Clinical Evidence ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Egfr Mutant

Epidermal growth factor receptor ( EGFR) gene mutations identify a molecularly defined subset of non-small cell lung cancer (NSCLC) patients who display an excellent sensitivity to EGFR tyrosine kinase inhibitors (TKIs). First-generation reversible EGFR TKIs, gefitinib and erlotinib have been proven to improve the objective response rate and to prolong the progression-free survival compared with standard chemotherapy in large phase III trials. Unfortunately, virtually all patients develop resistance to treatment, usually within 9–12 months. Afatinib is an irreversible ErbB family inhibitor initially designed to overcome the development of resistance. Compared with gefitinib in a first-line setting, afatinib prolonged progression-free survival and time to treatment failure, without impacting on overall survival in the general population of EGFR-mutant patients. However, afatinib has been shown to prolong overall survival in the subset of patients with an EGFR exon 19 deletion compared with chemotherapy. The aim of this review is to summarize the clinical evidence available to date and to critically discuss the place in therapy of afatinib in the rapidly expanding landscape of EGFR-mutant NSCLC first-line therapy.

Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9001-9001 ◽  
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Anuradha Chougule ◽  
Abhishek Mahajan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Egfr Mutant

9001 Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes. Methods: Phase III randomized trial in advanced chemotherapy-naïve NSCLC harboring EGFR sensitizing mutation (exon 19, 21 or 18) with performance status (PS) 0 to 2 planned for palliative therapy. Patients were stratified for PS and EGFR mutation and randomly assigned (computer-generated randomization by independent biostatistician) 1:1 to gefitinib 250 mg orally daily (gef) or gefitinib 250 mg orally daily with pemetrexed 500 mg/m2 IV and carboplatin AUC 5 IV every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 IV every 3 weeks (gef+C). Restaging was every 2 to 3 mths; therapy continued until progression or intolerable toxicity. Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Survival endpoints were assessed in the intention-to-treat population. Results: Between Aug 2016 and Aug 2018, 350 patients were randomly assigned to gef (n = 177) and gef+C (n = 173). Median age was 54 yrs, 48% were females, 84% never-smokers, 21% were PS 2 and 18% had brain metastases. Median follow-up in surviving patients was 17 months (range, 7 to 30). Radiologic response rates were 81% and 69% in gef+C and gef respectively, P = 0.012. 234 patients (67%) have had events for PFS, 98 in gef+C and 136 in gef. Estimated median PFS was significantly longer with gef+C than gef (16 months, [95% CI, 13.7 to 18.3] vs. 8 months [95% CI, 7.1 to 8.9]; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39 to 0.65; P < 0.001). 120 patients (34%) have died, 42 in gef+C and 78 in gef. Estimated median OS was significantly longer with gef+C than gef (not reached vs. 18 months [95% CI, 14.28 to 21.72]; hazard ratio for death, 0.45; 95% CI, 0.31 to 0.66; P < 0.001). Clinically relevant ≥ grade 3 toxicities occurred in 51% and 25% of patients in gef+C and gef arms respectively, P < 0.001. Conclusion: Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity. Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC. Clinical trial information: CTRI/2016/08/007149.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

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