Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

Roviello, Giandomenico; Zanotti, Laura; Cappelletti, Maria Rosa; Gobbi, Angela; Dester, Martina; Paganini, Giovanni; Pacifico, Chiara; Generali, Daniele; Roudi, Raheleh

doi:10.1007/s10238-017-0460-7

Cited by 44 publications

(20 citation statements)

References 27 publications

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“…Median PFS and median OS were 11.9 months and 20.9 months, respectively. These results are in line with previous studies performed in Asian elderly patients and with a recent meta-analysis [ 19 - 21 , 24 ].…”

Section: Discussionsupporting

confidence: 93%

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Octogenarians with EGFR-mutated non-small cell lung cancer treated by tyrosine-kinase inhibitor: a multicentric real-world study assessing tolerance and efficacy (OCTOMUT study)

et al. 2018

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ObjectiveTo assess efficacy and tolerance of EGFR tyrosine-kinase inhibitors (TKIs) for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in octogenarians.Patients and methodsPatients aged 80 years or older with EGFR-mutated NSCLC treated by EGFR TKI between January 2011 and March 2015 whatever the line of treatment were retrospectively selected.Results20 centers retrospectively included 114 patients (women, 77.2%; Caucasians, 98.3%; mean age, 83.9 years). A performance status of 0–1 or 2–3 at diagnosis was reported for 71.6% and 28.4% of patients, respectively. Overall, 95.6% of patients had adenocarcinomas and histological stage at diagnosis was stage IV for 79.8% of patients. EGFR mutations were identified mainly on exon 19 (46.5%) and exon 21 (40.4%). A geriatric assessment was performed in 35.1% of patients. TKI treatment was administered to 97.3% of patients as first or second line of treatment. Overall response rate and disease control rate were 63.3% (69/109) and 78.9% (86/109), respectively. Median progression-free survival was 11.9 months (95% confidence interval [CI], 8.6–14.7) and median overall survival was 20.9 months (95% CI, 14.3–27.1). After progression, 36/95 (37.9%) patients received a new line of chemotherapy. Main toxicities were cutaneous for 66.7% of patients (grade 3–4, 10%), diarrhea for 56.0% (grade 3–4, 15%; grade 5, 2%) and others for 25.7% (grade 3–4, 41%).ConclusionsOctogenarians with EGFR-mutated NSCLC treated by EGFR TKI had clinical outcomes and toxicity profile comparable to younger patients. Geriatric assessment appeared to be underused in this population.

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Section: Discussionsupporting

confidence: 93%

“…The meta-analysis of Roviello et al reported the pooled results of five clinical trials with the use of EGFR TKI in EGFR-mutated NSCLC in first line [ 24 ]. Four phase III studies and one phase IIb study were included in the analysis for a total of 1381 patients [ 15 , 18 , 25 - 27 ].…”

Section: Discussionmentioning

confidence: 99%

Octogenarians with EGFR-mutated non-small cell lung cancer treated by tyrosine-kinase inhibitor: a multicentric real-world study assessing tolerance and efficacy (OCTOMUT study)

et al. 2018

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“…Surgery, chemotherapy, radiotherapy, and targeted therapies are conventional lung cancer treatments [ 3 ]. Targeted therapies with tyrosine kinase inhibitors (TKIs) comprise epidermal growth factor receptor (EGFR) inhibitors, such as erlotinib or gefitinib, and anaplastic lymphoma kinase (ALK) inhibitors, such as crizotinib [ 4 , 5 ]. Considering the high mortality and morbidity rates of lung cancer and the emergence of drug resistance to chemoradiotherapy regimens and TKIs, determining targetable genetic changes is of paramount importance [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients

et al. 2018

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PurposeLung cancer is the deadliest known cancer in the world, with the highest number of mutations in proto-oncogenes and tumor suppressor genes. Therefore, this study was conducted to determine the status of hotspot regions in DDR2 and KRAS genes for the first time, as well as in TP53 gene, in lung cancer patients within the Iranian population.Experimental designThe mutations in exon 2 of KRAS, exon 18 of DDR2, and exons 5–6 of TP53 genes were screened in lung cancer samples, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) using PCR and sequencing techniques.ResultsAnalysis of the KRAS gene showed only a G12C variation in one large cell carcinoma (LCC) patient, whereas variants were not found in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases. The Q808H variation in the DDR2 gene was detected in one SCC sample, while no variant was seen in the ADC and LCC subtypes. Variations in the TP53 gene were seen in all NSCLC subtypes, including six ADC (13.63%), seven SCC (15.9%) and two LCC (4.54%). Forty-eight variants were found in the TP53 gene. Of these, 15 variants were found in coding regions V147A, V157F, Q167Q, D186G, H193R, T211T, F212L and P222P, 33 variants in intronic regions rs1625895 (HGVS: c.672+62A>G), rs766856111 (HGVS: c.672+6G>A) and two new variants (c.560-12A>G and c.672+86T>C).ConclusionsIn conclusion, KRAS, DDR2, and TP53 variants were detected in 2%, 2.17% and 79.54% of all cases, respectively. The frequency of DDR2 mutation is nearly close to other studies, while KRAS and TP53 mutation frequencies are lower and higher than other populations, respectively. Three new putative pathogenic variants, for the first time, have been detected in Iranian patients with lung cancer, including Q808H in DDR2, F212L, and D186G in coding regions of TP53. In addition, we observed five novel benign variants, including Q167Q, P222P and T211T in coding sequence, and c.560-12A>G and c.672+86T>C, in intronic region of TP53. Mutations of KRAS and DDR2 were found in LCC and SCC subtypes, respectively, whereas mutations of TP53 were seen in SCC and ADC subtypes with higher frequencies and LCC subtype with lower frequency. Therefore, Iranian lung cancer patients can benefit from mutational analysis before starting the conventional treatment. A better understanding of the biology of these genes and their mutations will be critical for developing future targeted therapies.

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“…There is accumulating evidence that TKIs may be more effective in elderly than in younger patients with EGFR mutation-positive NSCLC. 18,26 Moreover, given that kinase inhibitors usually show milder toxicity than cytotoxic chemotherapy, the current Japanese Lung Cancer Society guideline for stage IV NSCLC recommends (level 1C) the use of any EGFR TKI for the rst-line treatment of elderly patients with a driver oncogene. 17 In this regard, afatinib may be a suitable choice for elderly patients with EGFR mutationpositive NSCLC who are receiving multiple concomitant medications, due to its reported low potential for drug-drug interactions, and low exposure to hepatic metabolism and excretion.…”

Section: Discussionmentioning

confidence: 99%

“…1 Asian treatment guidelines also recommend EGFR TKI monotherapy as rst-line treatment for the general population of patients with EGFR mutation-positive NSCLC, 1,17 and there is evidence that EGFR TKIs may be effective for some elderly patients with EGFR mutation-positive NSCLC. 18 Indeed, in a subgroup analysis of the LUX-Lung 3, 6, and 7 studies, afatinib was effective and tolerable in patients with EGFR mutation-positive NSCLC, independent of age at diagnosis. 16 In addition to evidence from the LUX-Lung studies, a phase I trial including treatment at the approved dose of 40 mg, and a phase II trial employing afatinib 30 mg support the feasibility of rst-line afatinib as a treatment option in elderly Japanese patients with EGFR mutation-positive NSCLC.…”

Section: Introductionmentioning

confidence: 99%

A Phase II Study of First-line Afatinib For Patients Aged ≥ 75 Years With EGFR Mutation-positive Advanced Non-small Cell Lung Cancer: North East Japan Study Group Trial NEJ027

Minegishi

Yamaguchi

Sugawara

et al. 2020

Preprint

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Background: We investigated afatinib in elderly patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC).Patients and Methods: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥ 75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review.Results: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75–91), all patients had an Eastern Cooperative Oncology group performance status of 0 or 1, and 60.5% had Del19-positive disease. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5–19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2–not reached); the 2-year OS rate was 78.3%. The most common grade III/IV treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and 8 (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.Conclusion: First-line afatinib administered at a starting dose of 40 mg was well tolerated with dose adjustments and was associated with encouraging activity in Japanese patients aged ≥ 75 years with EGFR mutation-positive NSCLC.Trial Registration: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).

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Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

Cited by 44 publications

References 27 publications

Octogenarians with EGFR-mutated non-small cell lung cancer treated by tyrosine-kinase inhibitor: a multicentric real-world study assessing tolerance and efficacy (OCTOMUT study)

Octogenarians with EGFR-mutated non-small cell lung cancer treated by tyrosine-kinase inhibitor: a multicentric real-world study assessing tolerance and efficacy (OCTOMUT study)

Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients

A Phase II Study of First-line Afatinib For Patients Aged ≥ 75 Years With EGFR Mutation-positive Advanced Non-small Cell Lung Cancer: North East Japan Study Group Trial NEJ027

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