Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective against EGFR-mutant non-small-cell lung carcinoma but can cause serious adverse events, such as interstitial lung disease (ILD). Treatment strategies for osimertinib-induced ILD are not well established. Cytotoxic anticancer drugs are considered first, although several cases of successful rechallenge with EGFR-TKIs have been reported. We herein report a 67-year-old woman with symptomatic osimertinib-induced ILD who was switched to afatinib and later rechallenged with osimertinib and corticosteroids. Neither treatment resulted in ILD relapse, suggesting that these may be viable treatment options when alternative treatments are limited.
Keywords: epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib, interstitial lung disease (ILD), rechallenge, non-small-cell lung carcinoma (NSCLC)
Introduction
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have become the standard treatment for EGFR-mutant non-small-cell lung carcinoma (NSCLC), owing to their remarkable efficacy (1-3). Osimertinib, a third-generation EGFR-TKI, is particularly potent against both EGFR-sensitive and T790M-resistant mutations (4). Initially approved for T790M-resistant mutation NSCLC (5), it is now used as first-line therapy (6,7).
Interstitial lung disease (ILD) is a known adverse event of EGFR-TKIs. A higher incidence of EGFR-TKI-induced ILD has been reported in the Japanese population than in the global population. Among the EGFR-TKIs, osimertinib is associated with a higher incidence of ILD than first- and second-generation TKIs. In contrast, osimertinib-induced ILD is associated with a lower mortality rate than EGFR-TKI-induced ILD (8-18). Although several cases of successful rechallenge with EGFR-TKIs have been reported, no prospective clinical trial has examined EGFR-TKI rechallenge in patients with osimertinib-induced ILD, and the treatment strategies for osimertinib-induced ILD cases are not well established.
We herein report a case of osimertinib-induced ILD in a patient with lung adenocarcinoma, who was switched to afatinib and subsequently rechallenged with osimertinib and corticosteroids. We discuss potential treatment strategies for managing ILD in patients receiving osimertinib.
Case Report
A 67-year-old Japanese woman was referred to our hospital because of a mass in the right upper lung field. The patient had no relevant medical or smoking histories. Computed tomography (CT) revealed a 50-mm mass in the right upper lobe, multiple intrapulmonary nodules, an enlarged left adrenal gland, and osteolytic changes in the spine and the right iliac bone. High-resolution chest CT showed no interstitial changes in the lung fields. Lung adenocarcinoma was diagnosed with multiple brain, lung, bone, and adrenal metastases [cT2bN0M1c (BRA, PUL, OSS, ADR) and stage IVB] via an endobronchial biopsy, positron emission tomography-CT, and brain magnetic resonance imaging with contrast enhancement. Subsequently, an EGFR exon 19 deletion was detected.
Osimertinib (80 mg daily) was administered as first-line chemotherapy. The patient's performance status at the start of osimertinib treatment was 0. She presented to our clinic with dyspnea on exertion 42 days after starting osimertinib treatment. Her body temperature was 35.9°C, and her oxygen saturation, measured by pulse oximetry, was 94% on room air. A physical examination revealed no fine crackles on chest auscultation. An arterial blood gas analysis revealed a decrease in PaO2 (67.1 mmHg). Blood tests showed elevated serum levels of Krebs von den Lungen-6 (KL-6) (938 U/mL). The serum level of brain natriuretic peptide (BNP) was elevated (93.7 pg/mL) but did not show any substantial increase compared to the baseline level. Serum levels of β-D-glucan (＜2.5 pg/mL) and CMV-C10/C11 (negative) were not elevated.
She was diagnosed with grade 2 osimertinib-induced ILD, so osimertinib was discontinued, and treatment with prednisolone (PSL) was initiated (1.0 mg per kg, 40 mg daily). The ILD improved rapidly with steroid therapy, leading to tapering of the PSL dose. Once the PSL dose had been reduced to 10 mg daily, treatment with cytotoxic anticancer drugs was suggested. However, after fully explaining the risk of ILD relapse, she declined and was switched to a second-generation EGFR-TKI, afatinib (20 mg daily), as second-line chemotherapy. The patient's performance status at the start of afatinib treatment was 0. Thereafter, no ILD relapse or tumor reduction was observed, and the best response was a partial response. PSL was tapered off on day 119 of steroid therapy.
Eighteen months after starting afatinib, new intrapulmonary metastases appeared, and the patient developed progressive disease. Although we suggested several treatments with cytotoxic anticancer drugs, she continued afatinib at her request. Eleven months later, the multiple brain metastases worsened, prompting whole-brain irradiation (30 Gy in 10 fractions). Subsequently, the patient developed meningeal carcinomatosis.
A liquid biopsy for the EGFR genetic test detected a T790M resistance mutation. Despite being fully informed of the risk of ILD relapse, the patient and her family strongly desired rechallenge with osimertinib. Her performance status was 3 because of meningeal carcinomatosis and lack of alternative treatment; therefore, she was rechallenged with osimertinib 40 mg daily (half the standard dose) in combination with corticosteroids (PSL 0.5 mg/kg, and 20 mg daily). Following the osimertinib rechallenge, tumor reduction was achieved without ILD relapse.
Discussion
This report describes a case of successful switch to afatinib after osimertinib-induced ILD and a subsequent successful rechallenge with osimertinib combined with corticosteroids. EGFR-TKIs are highly effective against EGFR-mutant NSCLC. Osimertinib, a third-generation EGFR-TKI, is now used as first-line chemotherapy, demonstrating a significantly longer progression-free survival and overall survival in untreated EGFR-mutant NSCLC than with first-generation EGFR-TKIs (6,7).
However, EGFR-TKIs can cause ILD, which is a serious adverse event, and a particularly high incidence of ILD has been reported in the Japanese population. The reported frequencies of EGFR-TKI-induced ILD in Japanese patients are as follows: 3.2-4.0% for gefitinib (8-10), 2.8-4.9% for erlotinib (11-13), 3.7-4.4% for afatinib (14,15), and 6.8-18.3% for osimertinib (16-18), with osimertinib showing a higher frequency than others. In contrast, the mortality rates at ILD onset were 31.6-44.3% for gefitinib (8-10) and 33.3-40.0% for erlotinib (11-13), 0-17.1% for afatinib (14,15), and 0-11.8% for osimertinib (16-18). Notably, osimertinib-induced ILD is reported to have a low mortality rate because many patients with ILD present with frosted shadows and respond well to corticosteroids, which was also observed in this case.
Asymptomatic frosted shadows, known as transient asymptomatic pulmonary opacities (TAPO), frequently occur during treatment. In patients with TAPO, continued osimertinib therapy with careful follow-up is advocated (19). Therefore, the possibility of TAPO in osimertinib-induced ILD must be considered. However, in the present case, given the presence of frosted glass shadows in the bilateral lung fields during osimertinib treatment, along with dyspnea on exertion and a decrease in PaO2 on an arterial blood gas analysis, we judged that she had grade 2 osimertinib-induced ILD rather than TAPO; therefore, osimertinib was discontinued, and she was treated with corticosteroids.
In patients with EGFR-mutant NSCLC, sequential therapy including EGFR-TKIs and cytotoxic anticancer drugs is vital. When osimertinib-induced ILD develops, osimertinib is discontinued, and the patient is generally treated with cytotoxic anticancer drugs. In this case, cytotoxic anticancer drugs could not be administered because of the patient's strong preference. Rechallenge of EGFR-TKIs may be considered not only because of patient preference, as in this case, but also when other options are exhausted in sequential therapy, and the risks and benefits have been weighed.
Regarding EGFR-TKI rechallenge in patients with osimertinib-induced ILD, Imaji et al. reported that osimertinib was rechallenged in 33 patients with osimertinib-induced ILD during initial therapy, and 5 of these patients (15.2%) experienced relapse of ILD, suggesting that osimertinib rechallenge may be a treatment option (20). However, in that report, regarding the initial osimertinib-induced ILD, 26 of 33 patients developed grade 1 ILD, and only 5 of the 33 patients were treated with systemic steroids for ILD. Therefore, many patients with TAPO may have been included in that study. Kodama et al. also reported that osimertinib rechallenge may be an effective treatment option for grade 1 osimertinib-induced ILD (21). In contrast, Li et al. reported that 5 of 8 patients (62.5%) who were rechallenged with osimertinib for grade ≥2 symptomatic osimertinib-induced ILD experienced relapse of ILD, while only 1 of 9 patients (11.1%) who were switched to erlotinib experienced relapse of ILD (22).
Table shows previous case reports of rechallenge with EGFR-TKIs after osimertinib-induced ILD (23-35). Since the introduction of osimertinib as a first-line therapy, successful cases of switching to other EGFR-TKIs have been reported in patients with osimertinib-induced ILD without the T790M mutation. In these reports, switching to afatinib after osimertinib-induced ILD was achieved without relapse (31-33). It is reasonable to switch to afatinib because it has a lower incidence of ILD than osimertinib and a lower mortality rate than gefitinib and erlotinib. Based on the above findings, we suggest that osimertinib rechallenge is a feasible option for grade 1 osimertinib-induced ILD, whereas switching to afatinib is better for patients with grade ≥2 osimertinib-induced ILD without the T790M mutation.
Table.
Literature Review of Rechallenge with EGFR-TKIs after Osimertinib-induced ILD.
| Case | Age | Sex | EGFR mutation | Osimertinib dose | Time to onset | ILD grade | Rechallenge drug (dose) | Corticosteroid during rechallenge (dose) | Recurrence of ILD | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 38 | F | L858R, T790M | 80 mg | 31 days | NA | Osimertinib (80 mg daily) | No | No | (23) |
| 2 | 75 | F | Exon 19 deletion, T790M | 80 mg | 64 days | 2 | Osimertinib (40 mg daily) | Yes (PSL 0.5 mg/kg daily) | No | (24) |
| 3 | 62 | M | Exon 19 deletion, T790M | 80 mg | 82 days | 2 | Osimertinib (40 mg daily) | Yes (PSL 25 mg daily) | No | (25) |
| 4 | 82 | M | Exon 19 deletion, T790M | 80 mg | 8 months | 4 | Osimertinib (80 mg every other day>daily) | Yes (PSL 40 mg daily >off) | No | (26) |
| 5-1 | 60 | M | Exon 19 deletion, T790M | NA | 6 weeks | 3 | Osimertinib (NA) | No | Yes | (26) |
| 5-2 | 60 | M | Exon 19 deletion, T790M | NA | NA | 2 | Osimertinib (NA) | Yes (PSL 20 mg daily >off) | No | (26) |
| 6 | 69 | F | L858R, T790M | 80 mg | 55 days | 1 | Osimertinib (40 mg daily) | Yes (PSL 10 mg daily) | No | (27) |
| 7 | 57 | F | Exon 19 deletion, T790M | 80 mg | 3 weeks | 3 | Osimertinib (80 mg every other day>daily) | Yes (PSL 0.5 mg/kg daily >5 mg daily) | No | (28) |
| 8 | 75 | F | Exon 19 deletion, T790M | 80 mg | 6 months | 2 | Osimertinib (80 mg daily) | Yes (PSL 5 mg daily) | No | (29) |
| 9 | 71 | F | Exon 19 deletion | 80 mg | 1 week | 3 | Osimertinib (40 mg daily>80 mg daily) | No | No | (30) |
| 10-1 | NA | NA | NA | 80 mg | 155 days | 1 | Osimertinib (40 mg daily) | No | Yes | (31) |
| 10-2 | NA | NA | NA | 40 mg | NA | 1 | Afatinib (30 mg daily) | No | No | (31) |
| 11 | NA | NA | NA | 80 mg | 43 days | 2 | Afatinib (40 mg daily) | No | No | (31) |
| 12 | NA | NA | NA | 80 mg | 51 days | 3 | Afatinib (20 mg daily) | No | No | (31) |
| 13 | NA | NA | NA | 80 mg | 23 days | 1 | Afatinib (40 mg daily) | No | No | (31) |
| 14 | 78 | F | L858R | 80 mg | 4.5 months | 2 | Afatinib (30 mg daily) | No | No | (32) |
| 15 | 84 | F | Exon 19 deletion | 80 mg | 46 days | 3 | Afatinib (20 mg daily) | Yes (PSL 5 mg daily >off) | No | (33) |
| 16 | 81 | F | L858R | 80 mg | 44 days | 3 | Erlotinib (100 mg daily) | Yes (PSL 5 mg daily) | No | (34) |
| 17 | 62 | F | Exon 19 deletion | 80 mg | 69 days | 3 | Gefitinib (250 mg daily) | Yes (PSL 5 mg daily) | No | (35) |
| 18 | 82 | F | Exon 19 deletion | 80 mg | 7 days | 3 | Gefitinib (250 mg daily) | Yes (PSL 15 mg daily>5 mg daily) | No | (35) |
| 19-1 | 77 | M | L858R | 80 mg | 91 days | 2 | Osimertinib (40 mg daily) | No | Yes | (35) |
| 19-2 | 77 | M | L858R | 40 mg | 7 days | 2 | Gefitinib (250 mg daily) | No | Yes | (35) |
| 20 | 72 | F | L858R | 80 mg | 62 days | 3 | Gefitinib (250 mg daily) | No | No | (35) |
| 21 | 57 | F | L858R | 80 mg | 15 days | 2 | Gefitinib (250 mg daily) | Yes (PSL 30 mg daily >2.5 mg daily) | No | (35) |
| 22 | 78 | F | L858R | 80 mg | 51 days | 3 | Gefitinib (250 mg daily) | No | No | (35) |
| 23-1 | 67 | F | L858R | 80 mg | 42 days | 2 | Afatinib (20 mg daily) | Yes (PSL 10 mg daily >off) | No | Present case |
| 23-2 | 67 | F | L858R | 80 mg | 42 days | 2 | Osimertinib (40 mg daily) | Yes (PSL 20 mg daily >15 mg daily) | No | Present case |
M: male, F: female, EGFR: epidermal growth factor receptor, NA: not available, PSL: prednisolone
Conversely, several cases of successful osimertinib rechallenge during steroid reduction or maintenance therapy after osimertinib-induced ILD with no ILD relapse have been reported (24-27,29). Similar to our case, in a previous case, osimertinib was rechallenged with corticosteroids to prevent ILD relapse after completion of steroid therapy for osimertinib-induced ILD (28).
Two main mechanisms are involved in drug-induced lung injury - cytotoxic and immune (36) - and the mechanism of osimertinib-induced ILD is not yet clear; however, both mechanisms should be considered during osimertinib rechallenge. Given that lung injury by cytotoxic mechanisms is dose-dependent, osimertinib may be better administered at a reduced dose. In previous reports, patients were restarted at a lower dose than the usual dose; in some cases, the dose was increased to the usual dose after restarting at a reduced dose. In contrast, concomitant corticosteroids are effective in patients with lung injury caused by immune mechanisms. In patients who develop osimertinib-induced ILDs of grade ≥2, osimertinib should not be aggressively recommended because of the high risk of ILD relapse. However, if osimertinib rechallenge is unavoidable, a combination of corticosteroids should be considered, as relapse of ILD is likely to preclude additional treatment for NSCLC. In the present case, the steroid dosage was PSL 0.5 mg/kg, which is commonly used in the treatment of organizing pneumonia (25,28). However, long-term steroid treatment causes various side effects, including an increased risk of infection. Therefore, the appropriate dose and duration of steroid administration require further investigation, necessitating additional case accumulation.
Figure 1.
Chest radiography and computed tomography images. (A, B) Before osimertinib administration and (C, D) after 42 days of osimertinib treatment (at the time of osimertinib-induced interstitial lung disease).
Figure 2.
Clinical course and computed tomography of the progress. Interstitial lung disease (ILD) was observed 42 days after osimertinib administration; osimertinib was discontinued, and she was treated with steroids. After ILD improvement, afatinib was administered, and tumor reduction was achieved without relapse of ILD. Subsequently, tumor re-growth and a liquid biopsy revealed a T790M mutation. Osimertinib was rechallenged with corticosteroids, and tumor reduction was achieved without relapse of ILD.
Conclusions
We encountered a case of successful switching to afatinib after osimertinib-induced ILD, followed by successful rechallenge with osimertinib and corticosteroids. In patients with EGFR-mutant NSCLC, sequential therapy including EGFR-TKIs and cytotoxic anticancer drugs is vital. Even in patients with osimertinib-induced ILD, rechallenge with EGFR-TKIs should be considered after weighing the risks and benefits of sequential therapy. In such cases, osimertinib rechallenge is a feasible option for patients with grade 1 osimertinib-induced ILD, whereas switching to afatinib is better for patients with grade ≥2 osimertinib-induced ILD without the T790M mutation. Furthermore, for patients with osimertinib-induced ILDs of grade ≥2, osimertinib should not be aggressively recommended because of the high risk of ILD relapse. However, if osimertinib rechallenge is unavoidable, a combination of corticosteroids should be considered.
Author’s disclosure of potential Conflicts of Interest (COI).
Tomohiro Sakamoto: Honoraria, Eli Lilly Japan, AstraZeneca, and MSD.
Akira Ymasaaki: Honoraria, AstraZeneca, GlaxoSmithKline, and Sanofi.
References
- 1.Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362: 2380-2388, 2010. [DOI] [PubMed] [Google Scholar]
- 2.Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12: 735-742, 2011. [DOI] [PubMed] [Google Scholar]
- 3.Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31: 3327-3334, 2013. [DOI] [PubMed] [Google Scholar]
- 4.Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4: 1046-1061, 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376: 629-640, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-Mutated advanced non-small-cell lung cancer. N Engl J Med 378: 113-125, 2018. [DOI] [PubMed] [Google Scholar]
- 7.Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 382: 41-50, 2020. [DOI] [PubMed] [Google Scholar]
- 8.Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 24: 2549-2556, 2006. [DOI] [PubMed] [Google Scholar]
- 9.Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med 177: 1348-1357, 2008. [DOI] [PubMed] [Google Scholar]
- 10.Nakagawa M, Nishimura T, Teramukai S, et al. Interstitial lung disease in gefitinib-treated Japanese patients with non-small-cell lung cancer - a retrospective analysis: JMTO LC03-02. BMC Res Notes 2: 157, 2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Gemma A, Kudoh S, Ando M, et al. Final safety and efficacy of erlotinib in the phase 4 POLARSTAR surveillance study of 10 708 Japanese patients with non-small-cell lung cancer. Cancer Sci 105: 1584-1590, 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Goto K, Nishio M, Yamamoto N, et al. A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). Lung Cancer 82: 109-114, 2013. [DOI] [PubMed] [Google Scholar]
- 13.Atagi S, Katakami N, Yoshioka H, et al. Nested case control study of proteomic biomarkers for interstitial lung disease in Japanese patients with non-small-cell lung cancer treated with erlotinib: a multicenter phase IV study (JO21661). Clin Lung Cancer 14: 407-417, 2013. [DOI] [PubMed] [Google Scholar]
- 14.Kato T, Yoshioka H, Okamoto I, et al. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small-cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci 106: 1202-1211, 2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Tamura K, Nukiwa T, Gemma A, et al. Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small-cell lung cancer with daily afatinib. Int J Clin Oncol 24: 917-926, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Gemma A, Kusumoto M, Sakai F, et al. Real-world evaluation of factors for interstitial lung disease incidence and radiologic characteristics in patients with EGFR T790M-positive NSCLC treated with osimertinib in Japan. J Thorac Oncol 15: 1893-1906, 2020. [DOI] [PubMed] [Google Scholar]
- 17.Ohe Y, Imamura F, Nogami N, et al. Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset. Jpn J Clin Oncol 49: 29-36, 2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Kenmotsu H, Wakuda K, Mori K, et al. Randomized phase 2 study of osimertinib plus bevacizumab versus osimertinib for untreated patients with nonsquamous NSCLC harboring EGFR mutations: WJOG9717L study. J Thorac Oncol 17: 1098-1108, 2022. [DOI] [PubMed] [Google Scholar]
- 19.Noonan SA, Sachs PB, Camidge DR. Transient asymptomatic pulmonary opacities occurring during osimertinib treatment. J Thorac Oncol 11: 2253-2258, 2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Imaji M, Fujimoto D, Sato Y, et al. Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: a multicentre retrospective cohort study. Eur J Cancer 179: 15-24, 2023. [DOI] [PubMed] [Google Scholar]
- 21.Kodama H, Wakuda K, Yabe M, et al. Retrospective analysis of osimertinib rechallenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small-cell lung carcinoma. Invest New Drugs 39: 571-577, 2021. [DOI] [PubMed] [Google Scholar]
- 22.Li MSC, Lee KWC, Mok KKS, et al. Brief report: risk of recurrent interstitial lung disease from osimertinib versus erlotinib rechallenge after symptomatic osimertinib-induced interstitial lung disease. JTO Clin Res Rep 5: 100648, 2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Mamesaya N, Kenmotsu H, Takahashi T. Successful osimertinib rechallenge in a patient with advanced non-small-cell lung cancer following osimertinib-induced interstitial lung disease after treatment with nivolumab. Invest New Drugs 35: 839-841, 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Miyauchi E, Ichinose M, Inoue A. Successful osimertinib rechallenge in a patient with T790M-mutant non-small-cell lung cancer after osimertinib-induced interstitial lung disease. J Thorac Oncol 12: e59-e61, 2017. [DOI] [PubMed] [Google Scholar]
- 25.Kiriu T, Tamura D, Tachihara M, et al. Successful osimertinib rechallenge with steroid therapy after osimertinib-induced interstitial lung disease. Intern Med 57: 91-95, 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Nagasaka M, Gadgeel SM. Retreatment with osimertinib following pneumonitis. Clin Lung Cancer 19: e53-e55, 2018. [DOI] [PubMed] [Google Scholar]
- 27.Satoh S, Shiroyama T, Tamiya M, et al. Successful osimertinib rechallenge after osimertinib-induced pneumonitis in a patient with lung adenocarcinoma. Respir Med Case Rep 23: 68-70, 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Lu H, Dowell J. Osimertinib in pulmonary manifestations: two case reports and review of the literature. In Vivo 34: 315-319, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Itano J, Higo H, Ohashi K, et al. Successful re-administration of osimertinib in osimertinib-induced interstitial lung disease with an organizing pneumonia pattern: a case report and literature review. Intern Med 59: 823-828, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Mohammed T, Mangeshkar S, Rathmann J. Successful rechallenge with osimertinib after very acute onset of drug-induced pneumonitis. Case Rep Oncol 14: 733-738, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Nasu S, Suzuki H, Shiroyama T, et al. Safety and efficacy of afatinib for the treatment of non-small-cell lung cancer following osimertinib-induced interstitial lung disease: a retrospective study. Invest New Drugs 38: 1915-1920, 2020. [DOI] [PubMed] [Google Scholar]
- 32.Nishima S, Miyanaga A, Saito S, et al. Successful treatment with afatinib after osimertinib-induced interstitial lung disease in a patient with EGFR-mutant non-small-cell lung cancer. Intern Med 60: 591-594, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Sato Y, Sekine A, Hagiwara E, et al. Successful treatment with afatinib following the failure of osimertinib rechallenge with osimertinib-induced interstitial lung disease: a case report. Respir Med Case Rep 33: 101450, 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Fujimoto S, Katsurada N, Hazama D, Yamamoto M, Nagano T, Tachihara M. Successful treatment with ramucirumab plus erlotinib following osimertinib-induced interstitial lung disease. Intern Med 64: 749-751, 2025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Shimbu K, Hisakane K, Kadoma N, et al. Safety and efficacy of gefitinib administration after osimertinib-induced interstitial lung disease: a six-case series. OncoTargets Ther 17: 717-726, 2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Matsuno O. Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches. Respir Res 13: 39, 2012. [DOI] [PMC free article] [PubMed] [Google Scholar]