Research ArticleClinical Studies

Salvage Chemotherapy Following Osimertinib in Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation

MARI TONE, MINORU INOMATA, NOBUYASU AWANO, NAOYUKI KUSE, TATSUNORI JO, HANAKO YOSHIMURA, JONSU MINAMI, KOHEI TAKADA, SHINGO MIYAMOTO and TAKEHIRO IZUMO
Anticancer Research April 2020, 40 (4) 2239-2246; DOI: https://doi.org/10.21873/anticanres.14186

Abstract

Aim: The current study reports the type of salvage chemotherapy following osimertinib and its treatment efficacy in patients with non-small-cell lung carcinoma (NSCLC) who acquire resistance to osimertinib. Patients and Methods: In this retrospective cohort study, data from the medical charts of 40 patients with NSCLC treated with osimertinib were obtained, primarily focusing on 14 undergoing salvage chemotherapy including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) or cytotoxic agents immediately following osimertinib. The treatment efficacy of salvage chemotherapy was evaluated. Results: Five and nine patients received EGFR-TKI and cytotoxic agents following osimertinib, respectively. The overall response rate to EGFR-TKI treatment following osimertinib tended to be lower than that for cytotoxic agents (0% vs. 44.4%). The median progression-free-survival was significantly poorer in patients receiving EGFR-TKI treatment than in those receiving cytotoxic agents. Conclusion: Cytotoxic agent administration should be considered more frequently than EGFR-TKIs for patients with NSCLC resistant to osimertinib.

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are widely used for the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). Osimertinib, which is a third-generation EGFR-TKI, is especially useful, not only as second-line or later treatment, when lung cancer has acquired EGFR T790M mutation, but also as first-line therapy (1, 2). Osimertinib has good treatment efficacy for NSCLC harboring an EGFR mutation; the overall response rate (ORR) is 80%, and the median progression-free-survival (PFS) is reportedly 18.9 months in first-line therapy (2). Particularly in Japanese patients, however, the median overall survival (OS) using osimertinib as first-line therapy has been reported to be poorer than that using other EGFR-TKIs (3).

Almost all patients receiving EGFR-TKIs, including osimertinib, acquire resistance (4). The mechanism of resistance to osimertinib has been reported to be associated with mutations of EGFR such as C797X and L718V/Q, and of mesenchymal epithelial transition factor receptor (MET), and rearranged during transfection proto-oncogene gene (RET) (5-9). However, no effective therapeutic agent has been found for practical application.

A study in 2016 reported that 39.0% of patients with NSCLC harboring an EGFR mutation were re-administered EGFR-TKIs except for osimertinib (10). Several previous studies have also reported that re-administration of first- or second-generation EGFR-TKIs is a therapeutic option for patients with NSCLC who acquire resistance preceding therapy with those EGFR-TKIs (11-20). However, little is known concerning useful therapy for NSCLC resistance to osimertinib. Herein, we report what type of salvage chemotherapy we have used following osimertinib, osimertinib's treatment efficacy, and adverse events in patients with NSCLC who acquired resistance to osimertinib.

Patients and Methods

Patient selection and data collection. This retrospective cohort study included patients with stage IV, unresectable stage III, or postoperative recurrent EGFR-mutant NSCLC treated with osimertinib at the Japanese Red Cross Medical Center between June 2016 and July 2019. It mainly focused on patients undergoing salvage chemotherapy including EGFR-TKIs or cytotoxic agents immediately following therapy with osimertinib. Data were collected from the patients' medical charts. We collected data regarding baseline characteristics, treatment efficacy of osimertinib, salvage chemotherapy following osimertinib, and clinical courses until December 2019. Additionally, patients who received EGFR-TKIs or cytotoxic agents immediately following osimertinib were grouped into the EGFR-TKI group and the cytotoxic agent group, respectively, to evaluate treatment efficacy of salvage chemotherapy following osimertinib.

The efficacy of chemotherapy was evaluated based on ORR, PFS, and OS. The response to chemotherapy was assessed by the attending physician based on the Response Evaluation Criteria in Solid Tumors version 1 (21). PFS was defined as the time interval from initiation of each chemotherapy administration to the date of disease progression or death from any cause. OS was defined as the time from initiation of salvage chemotherapy to the date of death from any cause. Adverse events that occurred during the observation period were assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

Statistical analysis. ORRs to each treatment were compared using the chi-squared test. The PFS and OS curves were generated by the Kaplan–Meier method and compared using the log-rank test. The descriptive statistics presented in the current study included means, frequencies, and percentages. All reported p-values were two-sided, and p-values of less than 0.05 were considered statistically significant. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (the R Foundation for Statistical Computing, Vienna, Austria).

Ethical considerations. This retrospective study was approved by the Institutional Review Board of the Japanese Red Cross Medical Center (No. 1061) and was registered with the University Hospital Medical Information Network (UMIN 000039044). Due to the retrospective study design and based on the Japanese ethical guidelines for clinical research, the requirement for informed consent was waived.

Results

Baseline patient characteristics. A total of 40 patients were treated with osimertinib for advanced NSCLC at the study institution during the study period. Eleven and 29 patients were treated with osimertinib as first-line therapy and as second-line therapy or later, respectively (Figure 1). Of the 40 patients, 21 patients discontinued osimertinib. One and two patients discontinued osimertinib because of an adverse event and poorer general condition, respectively, and the remaining 18 patients discontinued because of demonstrated progression of their disease. Of the other 18 patients, 14 received salvage chemotherapy following osimertinib (EGFR-TKI group, N=5; cytotoxic agent group, N=9) and were included in the final analyses. In the EGFR-TKI group, gefitinib, and erlotinib were administered immediately after osimertinib to three and two patients, respectively. In the cytotoxic agents group, platinum doublets [combined with pemetrexed, N=3; combined with nab-paclitaxel, N=1; combined with atezolizumab, bevacizumab, and paclitaxel (ABCP), N=1] and monotherapy (TS-1, N=2; docetaxel, N=1; pemetrexed, N=1) were administered immediately after osimertinib to five and four patients, respectively. The baseline characteristics of the study cohort at the time of osimertinib treatment are summarized in Table I. All 14 patients who received salvage chemotherapy following osimertinib had adenocarcinoma harboring a major EGFR mutation, and 12 (85.7%) patients had it harboring a T790M mutation. Among these patients, two (14.3%) patients had received osimertinib as first-line therapy, and the others (75.7%) had received it as second-line or later. The median number of past treatment lines before osimertinib was two (range=0-5) in patients who received salvage chemotherapy following osimertinib. Patients in the cytotoxic agent group tended to receive fewer treatment lines before osimertinib therapy than those in the EGFR-TKI group [median of 1 (range=0-3) vs. 2 (range=1-5), respectively]. The median number of treatment lines after osimertinib was one (range 1-6) in those patients. In addition, patients in the EGFR-TKI group tended to receive fewer treatment lines after osimertinib than those in the cytotoxic agent group [median of 1 (range=1-3) vs. 2 (range=1-6), respectively].

Osimertinib treatment efficacy. The ORR to osimertinib was 64.3% in the patients who received salvage chemotherapy following osimertinib, and the median PFS in osimertinib was 10.0 months [95% confidence interval (CI)=4.0-18.0 months] (Table II). The ORR to osimertinib for the EGFR-TKI group tended to be lower than that for that treated with cytotoxic agents (40.0% vs. 77.8%, respectively; p=0.27). In addition, the median PFS for the EGFR-TKI group tended to be shorter than that for that treated with cytotoxic agents [9.0 months (95% CI=1.0 months-not reached) and 12.0 months (6.0 months-not reached); p=0.28].

Salvage chemotherapy following osimertinib treatment efficacy. In patients who received salvage chemotherapy following osimertinib, the ORR to salvage chemotherapy following osimertinib was 28.6% (Table III), and the median PFS and OS for salvage chemotherapy was 3.5 (95% CI=1.0-6.0) months and 8.0 months (95% CI=4.0 months-not reached), respectively. The ORR to salvage chemotherapy for the EGFR-TKI group tended to be lower than that for patients treated with cytotoxic agents (0% vs. 44.4%, respectively, p=0.22) (Table III). In addition, the ORR to platinum doublets following osimertinib tended to be higher than that to monotherapy following osimertinib (60% vs. 25%, respectively; p=0.52). Of note, a patient who received ABCP therapy showed good treatment efficacy (Figure 2).

The median duration of PFS after salvage chemotherapy for the EGFR-TKI group was significantly shorter than that for the cytotoxic agent group [2.0 (95% CI=1.0 months-not reached) vs. 5.0 (1.0-7.0) months, respectively] (Figure 3A). Similarly, the median OS after salvage chemotherapy for the EGFR-TKI group tended to be shorter than that for the cytotoxic agent group [6.0 (95% CI=2.0 months-not reached) vs. 19 (5.0-months-not reached), respectively (Figure 3B)].

Figure 1.
Figure 1.

Disposition of patients enrolled in the current study. EGFR: Epidermal growth factor receptor; TKI: tyrosine kinase inhibitor; PD: progressive disease; ICI: immune checkpoint inhibitor.

Adverse events in response to salvage chemotherapy following osimertinib. The incidence of all-grade adverse events in response to salvage chemotherapy was 42.9% (N=6); these events included neutropenia in three, thrombopenia in one, skin disorder in one, neuropathy in one, and anorexia in one (one patient had two adverse events). The incidence of grade 3 or poorer adverse events in salvage chemotherapy was 7.1% (N=1, neutropenia). All adverse events occurred in the group those with cytotoxic agents.

Clinical courses in patients receiving salvage chemotherapy following osimertinib and re-administration of osimertinib. Clinical courses after receiving osimertinib are depicted in Figure 4. Four (80%) out of five patients in the EGFR-TKI group received no chemotherapy after salvage chemotherapy following osimertinib (cases 10, and 12-14). Among all 14 patients receiving salvage chemotherapy following osimertinib, five (35.7%) in the cytotoxic agent group were re-administered osimertinib (cases 4-7, and 9), whereas no patient received it in the EGFR-TKI group. The median EGFR-TKI-free interval for receiving osimertinib treatment was 7 (range=3-17) months. The ORR to re-administration of osimertinib was 0% (the best treatment efficacy was reflected in two cases with stable disease and three with progressive disease).

Discussion

The current retrospective cohort study revealed that 35.7% of patients who had NSCLC harboring an EGFR mutation (N=5) received EGFR-TKIs immediately following osimertinib, and 64.3% of the rest (N=7) received cytotoxic agents. The ORR to EGFR-TKI treatment immediately following osimertinib was 0% and tended to be lower than that of cytotoxic agents. In addition, we found that the median PFS was significantly poorer in patients who received EGFR-TKI treatment immediately following osimertinib than in those who received cytotoxic agents.

View this table:
Table I.

Baseline characteristics of patients at the time of osimertinib therapy (N=40).

View this table:
Table II.

Efficacy of osimertinib (N=40).

In this study, there was no responder in the EGFR-TKI group, which included patients with NSCLC who received EGFR-TKIs immediately after osimertinib. In addition, the median PFS was short (2 months) in EGFR-TKI group. Past studies have reported the effectiveness of re-administration of EGFR-TKIs other than osimertinib following first- and second-generation EGFR-TKIs (11-20). The ORR to re-administration of EGFR-TKIs was reported to be 0%-36.0% (11-20), and the median PFS was reported to be 1.7-6.5 months (11-18). The treatment efficacies of EGFR-TKI re-administration were not good enough but it is considered to be a therapeutic option as salvage chemotherapy following EGFR-TKIs other than osimertinib.

The mechanism of resistance to osimertinib in relation to EGFR mutation is reported to be through C797X, L718Q, and G724S in first-line treatment and C797X, L718V/Q, G724S, G796X, and L792X in second-line or later treatment (5-8, 22). Because first- and second-generation EGFR-TKIs have been found to have efficacy in vitro against NSCLC harboring EGFR C797S and L718V/Q without T790M, first- and second-generation EGFR-TKIs might be useful for NSCLC resistant to osimertinib when it is not harboring T790M (8, 23-26). However, no study has reported the effectiveness of re-administration of osimertinib after disease progression in vivo, although several case reports reported its effectiveness after discontinuation of preceding osimertinib due to adverse events (27-29). Our results suggest that the treatment efficacy of osimertinib re-administration is not good for NSCLC which is resistant to osimertinib.

Figure 2.
Figure 2.

Computed tomographic findings of a patient who received combined atezolizumab, carboplatin, paclitaxel, and bevacizumab (ABCP) representing good treatment efficacy. a: A large tumor was located in the right upper lobe before receiving ABCP therapy. b: The tumor shrank after two courses of ABCP therapy.

Figure 3.
Figure 3.

Kaplan–Meier curves for progression-free (A) and overall (B) survival in patients with non-small cell lung cancer according to salvage chemotherapy immediately following osimertinib in groups treated with tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) or cytotoxic agents.

View this table:
Table III.

Efficacy of salvage chemotherapy following osimertinib.

Figure 4.
Figure 4.

Clinical courses after receiving osimertinib. ‘After salvage chemotherapy’ includes tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) and cytotoxic agents following salvage chemotherapy immediately after osimertinib. Cases 1 and 2 received osimertinib as first-line therapy. The remaining cases received osimertinib as second-line or later therapy. Five (35.7%) patients in the group treated with cytotoxic agents were re-administered osimertinib.

The treatment efficacy of platinum doublet for lung cancer harboring an EGFR mutation is poorer than that of EGFR-TKIs; however, a previous study reported that approximately half of patients who had lung cancer harboring an EGFR mutation received platinum doublets after acquiring resistance to EGFR-TKIs (10). A recent report showed that the treatment efficacy of ABCP therapy was good for patients with lung adenocarcinoma harboring an EGFR mutation (30). In our study, the ORR to platinum doublet therapy including ABCP therapy following osimertinib tended to be high (60%). Adverse events occurred in almost all the patients who received cytotoxic agents; however, there was no uncontrollable event. These results suggest that cytotoxic agents, especially platinum doublet therapy including ABCP, should be considered for administration to patients who have lung cancer with osimertinib resistance and good Eastern Cooperative Oncology Group performance status.

Past studies regarding the re-administration of EGFR-TKIs reported factors influencing good response to re-administration of EGFR-TKIs, including the EGFR-TKI-free interval (18-20). However, there was no responder among patients who received re-administration of osimertinib after a median osimertinib-free interval of 7 months from it in this current study. These results might suggest that re-administration of osimertinib should not be considered even after an osimertinib-free interval.

The limitations of this study include its small sample size. Additionally, this was a retrospective study performed at a single institution, including a heterogenous cohort of patients treated with osimertinib who were administered osimertinib as first- or later-line treatment. A large-scale prospective cohort study is warranted to further elucidate the optimal choice of salvage chemotherapy following osimertinib.

In conclusion, the treatment efficacy of salvage chemotherapy immediately following osimertinib was better in patients who received cytotoxic agents than in those who received EGFR-TKIs. Cytotoxic agents, especially platinum doublet therapy including ABCP therapy, should be considered more frequently than EGFR-TKIs for administration to patients with NSCLC resistant to osimertinib.

Acknowledgements

The Authors would like to thank Enago (www.enago.jp) for English language review.

Footnotes

  • Authors' Contributions

    Mari Tone, Minoru Inomata and Takehiro Izumo performed the analyzed the data, and wrote the article. Mari Tone, Nobuyasu Awano, Naoyuki Kuse, Tatsunori Jo, Hanako Yoshimura, Jonsu Minami and Kohei Takada performed the literature review and acquisition of data. Shingo Miyamoto and Takehiro Izumo supervised the study. All Authors conceived and designed the study and gave final approval for publication.

  • Conflicts of Interest

    The Authors have no conflicts of interest to declare.

  • Received February 1, 2020.
  • Revision received February 12, 2020.
  • Accepted February 18, 2020.

References

  1. ↵
    1. Mok TS,
    2. Wu YL,
    3. Ahn MJ,
    4. Garassino MC,
    5. Kim HR,
    6. Ramalingam SS,
    7. Shepherd FA,
    8. He Y,
    9. Akamatsu H,
    10. Theelen WS,
    11. Lee CK,
    12. Sebastian M,
    13. Templeton A,
    14. Mann H,
    15. Marotti M,
    16. Ghiorghiu S,
    17. Papadimitrakopoulou VA,
    18. AURA3 Investigators
    : Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376(7): 629-640, 2017. PMID: 27959700. DOI: 10.1056/NEJMoa1612674
    OpenUrlCrossRefPubMed
  2. ↵
    1. Soria JC,
    2. Ohe Y,
    3. Vansteenkiste J,
    4. Reungwetwattana T,
    5. Chewaskulyong B,
    6. Lee KH,
    7. Dechaphunkul A,
    8. Imamura F,
    9. Nogami N,
    10. Kurata T,
    11. Okamoto I,
    12. Zhou C,
    13. Cho BC,
    14. Cheng Y,
    15. Cho EK,
    16. Voon PJ,
    17. Planchard D,
    18. Su WC,
    19. Gray JE,
    20. Lee SM,
    21. Hodge R,
    22. Marotti M,
    23. Rukazenkov Y,
    24. Ramalingam SS,
    25. FLAURA Investigators
    : Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378(2): 113-125, 2018. PMID: 29151359. DOI: 10.1056/NEJMoa1713137
    OpenUrlCrossRefPubMed
  3. ↵
    1. Nogami N,
    2. Ramalingam SS,
    3. Imamura F,
    4. Okamoto I,
    5. Kurata T,
    6. Kato T,
    7. Sugawara S,
    8. Nakagawa K,
    9. Uchida H,
    10. Hodge R,
    11. Saggese M,
    12. Walding A,
    13. Ohe Y
    : Osimertinib as first-line therapy for EGFRm advanced NSCLC (FLAURA): Final OS in Japanese subset. Jpn J Lung Cancer PS-1, 2019. Available at: https://www.haigan.gr.jp/journal/am/2019a/19a_pdsy0000PS-1.html
  4. ↵
    1. Jackman D,
    2. Pao W,
    3. Riely GJ,
    4. Engelman JA,
    5. Kris MG,
    6. Jänne PA,
    7. Lynch T,
    8. Johnson BE,
    9. Miller VA
    : Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 28(2): 357-360, 2010. PMID: 19949011. DOI: 10.1200/JCO.2009.24.7049
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Yang Z,
    2. Yang N,
    3. Ou Q,
    4. Xiang Y,
    5. Jiang T,
    6. Wu X,
    7. Bao H,
    8. Tong X,
    9. Wang X,
    10. Shao YW,
    11. Liu Y,
    12. Wang Y,
    13. Zhou C
    : Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients. Clin Cancer Res 24(13): 3097-3107, 2018. PMID: 29506987. DOI: 10.1158/1078-0432.CCR-17-2310
    OpenUrlAbstract/FREE Full Text
    1. Brown BP,
    2. Zhang YK,
    3. Westover D,
    4. Yan Y,
    5. Qiao H,
    6. Huang V,
    7. Du Z,
    8. Smith JA,
    9. Ross JS,
    10. Miller VA,
    11. Ali S,
    12. Bazhenova L,
    13. Schrock AB,
    14. Meiler J,
    15. Lovly CM
    : On-target resistance to the mutant-selective EGFR inhibitor osimertinib can develop in an allele-specific manner dependent on the original EGFR-activating mutation. Clin Cancer Res 25(11): 3341-3351, 2019. PMID: 30796031. DOI: 10.1158/1078-0432.CCR-18-3829
    OpenUrlAbstract/FREE Full Text
    1. Le X,
    2. Puri S,
    3. Negrao MV,
    4. Nilsson MB,
    5. Robichaux J,
    6. Boyle T,
    7. Hicks JK,
    8. Lovinger KL,
    9. Roarty E,
    10. Rinsurongkawong W,
    11. Tang M,
    12. Sun H,
    13. Elamin Y,
    14. Lacerda LC,
    15. Lewis J,
    16. Roth JA,
    17. Swisher SG,
    18. Lee JJ,
    19. William WN Jr.,
    20. Glisson BS,
    21. Zhang J,
    22. Papadimitrakopoulou VA,
    23. Gray JE,
    24. Heymach JV
    : Landscape of EGFR-dependent and -independent resistance mechanisms to osimertinib and continuation therapy beyond progression in EGFR-mutant NSCLC. Clin Cancer Res 24(24): 6195-6203, 2018. PMID: 30228210. DOI: 10.1158/1078-0432.CCR-18-1542
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Nishino M,
    2. Suda K,
    3. Kobayashi Y,
    4. Ohara S,
    5. Fujino T,
    6. Koga T,
    7. Chiba M,
    8. Shimoji M,
    9. Tomizawa K,
    10. Takemoto T,
    11. Mitsudomi T
    : Effects of secondary EGFR mutations on resistance against upfront osimertinib in cells with EGFR-activating mutations in vitro. Lung Cancer 126: 149-155, 2018. PMID: 30527179. DOI: 10.1016/j.lungcan.2018.10.026
    OpenUrlPubMed
  9. ↵
    1. Piotrowska Z,
    2. Isozaki H,
    3. Lennerz JK,
    4. Gainor JF,
    5. Lennes IT,
    6. Zhu VW,
    7. Marcoux N,
    8. Banwait MK,
    9. Digumarthy SR,
    10. Su W,
    11. Yoda S,
    12. Riley AK,
    13. Nangia V,
    14. Lin JJ,
    15. Nagy RJ,
    16. Lanman RB,
    17. Dias-Santagata D,
    18. Mino-Kenudson M,
    19. Iafrate AJ,
    20. Heist RS,
    21. Shaw AT,
    22. Evans EK,
    23. Clifford C,
    24. Ou SI,
    25. Wolf B,
    26. Hata AN,
    27. Sequist LV
    : Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. Cancer Discov 8(12): 1529-1539, 2018. PMID: 30257958. DOI: 10.1158/2159-8290.CD-18-1022
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Inoue A,
    2. Yoshida K,
    3. Morita S,
    4. Imamura F,
    5. Seto T,
    6. Okamoto I,
    7. Nakagawa K,
    8. Yamamoto N,
    9. Muto S,
    10. Fukuoka M
    : Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: A retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 46(5): 462-467, 2016. PMID: 26977054. DOI: 10.1093/jjco/hyw014
    OpenUrlCrossRefPubMed
  11. ↵
    1. Cappuzzo F,
    2. Morabito A,
    3. Normanno N,
    4. Bidoli P,
    5. Del Conte A,
    6. Giannetta L,
    7. Montanino A,
    8. Mazzoni F,
    9. Buosi R,
    10. Burgio MA,
    11. Cerea G,
    12. Chiari R,
    13. Cortinovis D,
    14. Finocchiaro G,
    15. Foltran L,
    16. Migliorino MR,
    17. Tiseo M,
    18. Ferrari S,
    19. De Marinis F
    : Efficacy and safety of rechallenge treatment with gefitinib in patients with advanced non-small cell lung cancer. Lung Cancer 99: 31-37, 2016 . PMID: 27565910. DOI: 10.1016/j.lungcan.2016.06.008
    OpenUrlPubMed
    1. Asahina H,
    2. Oizumi S,
    3. Inoue A,
    4. Kinoshita I,
    5. Ishida T,
    6. Fujita Y,
    7. Sukoh N,
    8. Harada M,
    9. Maemondo M,
    10. Saijo Y,
    11. Dosaka-Akita H,
    12. Isobe H,
    13. Nukiwa T,
    14. Nishimura M,
    15. Hokkaido Lung Cancer Clinical Study Group
    : Phase II study of gefitinib re-administration in patients with advanced non-small cell lung cancer and previous response to gefitinib. Oncology 79(5-6): 423-429, 2010. PMID: 21474967. DOI: 10.1159/000326488
    OpenUrlCrossRefPubMed
    1. Cho KM,
    2. Keam B,
    3. Kim TM,
    4. Lee SH,
    5. Kim DW,
    6. Heo DS
    : Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure. Korean J Intern Med 30(6): 891-898, 2015. PMID: 26552465. DOI: 10.3904/kjim.2015.30.6.891
    OpenUrlPubMed
    1. Koizumi T,
    2. Agatsuma T,
    3. Ikegami K,
    4. Suzuki T,
    5. Kobayashi T,
    6. Kanda S,
    7. Yoshikawa S,
    8. Kubo K,
    9. Shiina T,
    10. Takasuna K,
    11. Matsuo A,
    12. Hayasaka M,
    13. Morikawa M,
    14. Ameshima S
    : Prospective study of gefitinib re-administration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib. Clin Lung Cancer 13(6): 458-463, 2012. PMID: 22402083. DOI: 10.1016/j.cllc.2012.01.006
    OpenUrlCrossRefPubMed
    1. Becker A,
    2. Crombag L,
    3. Heideman DA,
    4. Thunnissen FB,
    5. van Wijk AW,
    6. Postmus PE,
    7. Smit EF
    : Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer 47(17): 2603-2606, 2011. PMID: 21784628. DOI: 10.1016/j.ejca.2011.06.046
    OpenUrlCrossRefPubMed
    1. Oh IJ,
    2. Ban HJ,
    3. Kim KS,
    4. Kim YC
    : Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: A single-arm, open-label, phase II study. Lung Cancer 77(1): 121-127, 2012. PMID: 22333554. DOI: 10.1016/j.lungcan.2012.01.012
    OpenUrlCrossRefPubMed
    1. Watanabe S,
    2. Tanaka J,
    3. Ota T,
    4. Kondo R,
    5. Tanaka H,
    6. Kagamu H,
    7. Ichikawa K,
    8. Koshio J,
    9. Baba J,
    10. Miyabayashi T,
    11. Narita I,
    12. Yoshizawa H
    : Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: A retrospective analysis. BMC Cancer 11: 1, 2011. PMID: 21194487. DOI: 10.1186/1471-2407-11-1
    OpenUrlCrossRefPubMed
  18. ↵
    1. Costa DB,
    2. Nguyen KS,
    3. Cho BC,
    4. Sequist LV,
    5. Jackman DM,
    6. Riely GJ,
    7. Yeap BY,
    8. Halmos B,
    9. Kim JH,
    10. Jänne PA,
    11. Huberman MS,
    12. Pao W,
    13. Tenen DG,
    14. Kobayashi S
    : Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 14(21): 7060-7067, 2008. PMID: 18981003. DOI: 10.1158/1078-0432.CCR-08-1455
    OpenUrlAbstract/FREE Full Text
    1. Kaira K,
    2. Naito T,
    3. Takahashi T,
    4. Ayabe E,
    5. Shimoyama R,
    6. Kaira R,
    7. Ono A,
    8. Igawa S,
    9. Shukuya T,
    10. Murakami H,
    11. Tsuya A,
    12. Nakamura Y,
    13. Endo M,
    14. Yamamoto N
    : Pooled analysis of the reports of erlotinib after failure of gefitinib for non-small cell lung cancer. Lung Cancer 68(1): 99-104, 2010. PMID: 19540616. DOI: 10.1016/j.lungcan.2009.05.006
    OpenUrlCrossRefPubMed
  20. ↵
    1. Tomizawa Y,
    2. Fujita Y,
    3. Tamura A,
    4. Shirai M,
    5. Shibata S,
    6. Kawabata T,
    7. Shibayama T,
    8. Fukai S,
    9. Kawahra M,
    10. Saito R
    : Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy. Lung Cancer 68(2): 269-272, 2010. PMID: 19660826. DOI: 10.1016/j.lungcan.2009.06.025
    OpenUrlCrossRefPubMed
  21. ↵
    1. Eisenhauer EA,
    2. Therasse P,
    3. Bogaerts J,
    4. Schwartz LH,
    5. Sargent D,
    6. Ford R,
    7. Dancey J,
    8. Arbuck S,
    9. Gwyther S,
    10. Mooney M,
    11. Rubinstein L,
    12. Shankar L,
    13. Dodd L,
    14. Kaplan R,
    15. Lacombe D,
    16. Verweij J
    : New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228-247, 2009. PMID: 19097774. DOI: 10.1016/j.ejca.2008.10.026
    OpenUrlCrossRefPubMed
  22. ↵
    1. Ou SI,
    2. Cui J,
    3. Schrock AB,
    4. Goldberg ME,
    5. Zhu VW,
    6. Albacker L,
    7. Stephens PJ,
    8. Miller VA,
    9. Ali SM
    : Emergence of novel and dominant acquired EGFR solvent-front mutations at Gly796 (G796S/R) together with C797S/R and L792F/H mutations in one EGFR (L858R/T790M) NSCLC patient who progressed on osimertinib. Lung Cancer 108: 228-231, 2017. PMID: 28625641. DOI: 10.1016/j.lungcan.2017.04.003
    OpenUrlCrossRefPubMed
  23. ↵
    1. Ayeni D,
    2. Politi K,
    3. Goldberg SB
    : Emerging agents and new mutations in EGFR-mutant lung cancer. Clin Cancer Res 21(17): 3818-3820, 2015. PMID: 26169963. DOI: 10.1158/1078-0432.CCR-15-1211
    OpenUrlAbstract/FREE Full Text
    1. Ercan D,
    2. Choi HG,
    3. Yun CH,
    4. Capelletti M,
    5. Xie T,
    6. Eck MJ,
    7. Gray NS,
    8. Jänne PA
    : EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors. Clin Cancer Res 21(17): 3913-3923, 2015. PMID: 25948633. DOI: 10.1158/1078-0432.CCR-14-2789
    OpenUrlAbstract/FREE Full Text
    1. Niederst MJ,
    2. Hu H,
    3. Mulvey HE,
    4. Lockerman EL,
    5. Garcia AR,
    6. Piotrowska Z,
    7. Sequist LV,
    8. Engelman JA
    : The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin Cancer Res 21(17): 3924-3933, 2015. PMID: 25948633. DOI: 10.1158/1078-0432.CCR-14-2789
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Liu Y,
    2. Li Y,
    3. Ou Q,
    4. Wu X,
    5. Wang X,
    6. Shao YW,
    7. Ying J
    : Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell lung cancer but retains sensitivity to afatinib. Lung Cancer 118: 1-5, 2018. PMID: 29571986. DOI: 10.1016/j.lungcan.2018.01.015.
    OpenUrlCrossRefPubMed
  27. ↵
    1. Yoshida H,
    2. Kim YH
    : Successful osimertinib rechallenge after severe osimertinib-induced hepatotoxicity. J Thorac Oncol 12(5): e61-63, 2017. PMID: 28291724. DOI: 10.1016/j.jtho.2017.01.026
    OpenUrlPubMed
    1. Kiriu T,
    2. Tamura D,
    3. Tachihara M,
    4. Sekiya R,
    5. Hazama D,
    6. Katsurada M,
    7. Nakata K,
    8. Nagano T,
    9. Yamamoto M,
    10. Kamiryo H,
    11. Kobayashi K,
    12. Nishimura Y
    : Successful osimertinib rechallenge with steroid therapy after osimertinib-induced interstitial lung disease. Intern Med 57(1): 91-95, 2018. PMID: 29033419. DOI: 10.2169/internalmedicine.8947-17
    OpenUrlPubMed
  29. ↵
    1. Miyauchi E,
    2. Ichinose M,
    3. 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(5): e59-61, 2017. PMID: 28434520. DOI: 10.1016/j.jtho.2017.01.027
    OpenUrlPubMed
  30. ↵
    1. Reck M,
    2. Mok TSK,
    3. Nishio M,
    4. Jotte RM,
    5. Cappuzzo F,
    6. Orlandi F,
    7. Stroyakovskiy D,
    8. Nogami N,
    9. Rodríguez-Abreu D,
    10. Moro-Sibilot D,
    11. Thomas CA,
    12. Barlesi F,
    13. Finley G,
    14. Lee A,
    15. Coleman S,
    16. Deng Y,
    17. Kowanetz M,
    18. Shankar G,
    19. Lin W,
    20. Socinski MA,
    21. IMpower150 Study Group
    : Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med 7(5): 387-401, 2019. PMID: 30922878. DOI: 10.1016/S2213-2600(19)30084-0
    OpenUrlPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Salvage Chemotherapy Following Osimertinib in Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation
MARI TONE, MINORU INOMATA, NOBUYASU AWANO, NAOYUKI KUSE, TATSUNORI JO, HANAKO YOSHIMURA, JONSU MINAMI, KOHEI TAKADA, SHINGO MIYAMOTO, TAKEHIRO IZUMO
Anticancer Research Apr 2020, 40 (4) 2239-2246; DOI: 10.21873/anticanres.14186
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords