|
 
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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 18
| Issue : 2 | Page : 516-524 |
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Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-rearrangement non-small-cell lung cancer patients with brain metastases in China
Zhixin Qiu1, Xinhong Xian2, Chunrong Liu3, Min Yu4, Feng Lin5, Meijuan Huang4, Ke Wang6
1 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Sichuan Province, Chengdu, P.R. China
2 West China Clinical Medical College, Sichuan University, Sichuan Province, Chengdu, P.R. China
3 Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Sichuan Province, Chengdu, P.R. China
4 Department of Chest Oncology, West China Hospital, Sichuan University, Sichuan Province, Chengdu, P.R. China
5 Department of Thoracic Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, P.R. China
6 Department of Respiratory and Critical Care Medicine; Lung Cancer Treatment Center, West China Hospital, Sichuan University, Sichuan Province, Chengdu, P.R. China
| Date of Submission | 25-Aug-2021 |
| Date of Decision | 08-Mar-2022 |
| Date of Acceptance | 10-Mar-2022 |
| Date of Web Publication | 20-May-2022 |
Correspondence Address:
Ke Wang
Department of Respiratory and Critical Care Medicine, Lung Cancer Treatment Center, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041
P.R. China
Meijuan Huang
Department of Chest Oncology, West China Hospital, Sichuan University, Sichuan Province, Chengdu
P.R. China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcrt.jcrt_1453_21
Objectives: The real-world intracranial efficacy data of ceritinib at a dose of 450 mg quaque die (QD) are currently unavailable. Therefore, we evaluated the intracranial efficacy of ceritinib (450 mg QD) in anaplastic lymphoma kinase (ALK)-rearrangement NSCLC patients in China.
Materials and Methods: In total, 57 ALK-rearrangement NSCLC patients with brain metastases (BM) were enrolled retrospectively in this real-world study. Of these, 53 patients experienced progression at baseline during or after prior crizotinib administration, and 24 patients received prior brain radiotherapy. Patients received ceritinib (450 mg QD) treatment. Intracranial efficacy [objective response rate (ORR) and disease control rate (DCR)] was evaluated according to the Response Assessment in Neuro-Oncology (RANO) standard; progression-free survival (PFS) and adverse events (AEs) data were obtained through follow-ups.
Results: The intracranial ORR and DCR of ceritinib were 73.7% and 93.0%, respectively. The median intracranial PFS in patients reaching the endpoint was 8.75 months, whereas the median intracranial PFS in all patients was not reached and predicted to be not evaluable (NE) (95% CI: 12.9–NE). The estimated 12-month event-free probability (EFP) of intracranial lesions was 68.1%. A subgroup analysis revealed that the estimated 12-month EFP of intracranial lesions was relatively higher in patients with prior brain radiotherapy (93.8% vs. 47.1%, P = 0.0006).
Conclusion: Ceritinib administered at 450 mg QD to ALK-rearrangement NSCLC patients with BM in China exhibited superior ORR and DCR, as well as PFS and event free probability. The estimated 12-month EFP for intracranial lesions improved in patients with prior brain radiotherapy.
Keywords: ALK, ceritinib, main metastases, NSCLC, real world
How to cite this article:
Qiu Z, Xian X, Liu C, Yu M, Lin F, Huang M, Wang K. Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-rearrangement non-small-cell lung cancer patients with brain metastases in China. J Can Res Ther 2022;18:516-24 |
How to cite this URL:
Qiu Z, Xian X, Liu C, Yu M, Lin F, Huang M, Wang K. Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-rearrangement non-small-cell lung cancer patients with brain metastases in China. J Can Res Ther [serial online] 2022 [cited 2022 Jul 7];18:516-24. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/516/345525 |
| > Introduction | |  |
Lung cancer is a neoplasm known to have the highest prevalence and mortality rate in the world; approximately 85% of the cases of lung cancer are non-small cell lung cancer (NSCLC). Because of the lack of effective methods for early diagnosis, 70%–80% of patients lose the chance for surgery at the time of diagnosis.[1] Currently, chemotherapy, targeted therapy, and immunotherapy are the main non-surgical systemic therapies for NSCLC.
Since the concept of precision medicine was first proposed in 2011, targeted therapy has become a new strategy for the treatment of advanced NSCLC patients with positive driver genes. The rearrangement of anaplastic lymphoma kinase (ALK), which is a molecular subtype and major driver gene of lung cancer, occurs in approximately 5% of NSCLCs, primarily in adenocarcinomas.[2],[3] The efficacy of the first-generation ALK tyrosine kinase inhibitor (TKI), that is, crizotinib, for the treatment of advanced ALK-rearrangement NSCLC has been demonstrated in a series of PROFILE trials.[4],[5] However, all patients inevitably develop resistance, which has prompted the development of second-generation TKIs, such as ceritinib and alectinib. Ceritinib, an oral TKI with high selectivity, exhibits significant inhibitory effects on the growth of crizotinib-resistant tumor cells as demonstrated in preclinical studies.[6] The phase I/II clinical studies, ASCEND-1 and ASCEND-2, have preliminarily confirmed that ceritinib administered at the maximum tolerated dose of 750 mg quaque die (QD, once a day) under fasting condition shows good efficacy for the treatment of ALK-rearrangement NSCLC.[7],[8] Based on the ASCEND-4 and ASCEND-5 studies and compared with conventional chemotherapy, ceritinib significantly prolongs progression-free survival (PFS) (ASCEND-5: 1.6 months vs. 5.4 months and ASCEND-4: 8.1 months vs. 16.6 months) in ALK-positive NSCLC patients after crizotinib failure or in first-line treatment.[9],[10] Its efficacy in lung cancer patients with brain metastases (BM) is also of interest to clinicians. Approximately 30%–50% of ALK-rearrangement NSCLC patients have BM, which portend a poor prognosis.[11],[12],[13] Crizotinib is approved for ALK + NSCLC patients; however, acquired resistance often develops after 1–2 years in patients, and brain progression frequently occurs.[4],[5],[14],[15] Ceritinib has shown promising intracranial antitumor activity in several studies.[7],[16] Another factor for clinical practice is the safety of ceritinib, which can affect patient compliance with treatment, thus affecting its overall efficacy. In previous studies, a high proportion of gastrointestinal (GI) disturbances, such as diarrhea, nausea, and vomiting, were observed when ceritinib was administered at a dose of 750 mg QD under fasting condition. Due to these side effects, 69.3%–80% of patients had to have their treatment adjusted, delayed, or even interrupted. To improve patient compliance during treatment, the ASCEND-8 study evaluated the mode of administration of ceritinib. As a result, a dose of 750 mg QD under fasting condition or 450 mg QD under fed condition yielded similar pharmacokinetics, whereas the latter was observed to improve the efficacy and significantly enhance GI tolerability (ORR: 78.1% vs. 75.7%, DOR: not reached vs. 15.4 months, and PFS: not reached vs. 12.2 months).[17],[18] However, the studies described above were performed with Korean and Caucasian patients; thus, the impact on other ethnic populations remains unclear.
On May 31, 2018, China granted approval to ceritinib for the treatment of advanced ALK-rearrangement NSCLC patients who are intolerant of or experience disease progression following treatment with crizotinib. Subsequently, on May 28, 2020, ceritinib was approved for first-line treatment of ALK-rearrangement NSCLC patients in China. With the widespread use of ceritinib, establishing real-world data with respect to its efficacy in Chinese patients is deemed important. Although the ASCEND-7 reported intracranial efficacy data at 750 mg QD under fasting condition, data for 450 mg QD under fed condition remain unavailable.[16] Therefore, in the present study, we have determined the intracranial efficacy of ceritinib (450 mg QD under fed condition) in Chinese patients.
| > Methods | | |
Patient Information
In total, 57 ALK-rearrangement NSCLC patients with BM were enrolled from several hospitals in Sichuan including West China Hospital, Affiliated Hospital of Chengdu University, Chengdu Third People's Hospital, Chengdu Seventh People's Hospital, Yibin Second People's Hospital, and Leshan Hospital of Traditional Chinese Medicine from October 2018 to May 2020 and were reviewed retrospectively for this study. All patients received ceritinib 450 mg QD under fed condition during all lines. All patients were administered ceritinib orally until disease progression, drug intolerance, patient refusal, or death. We obtained the approval from Ethics Committee on Biomedical Research, West China Hospital of Sichuan University at the date of 2020.7.28.
Through the electronic medical record system, standard patient clinical characteristics and prior treatment data, such as gender, age, Eastern Cooperative Oncology Group (ECOG) performance status score, smoking history, pathological type, TNM stage, metastasis site, and gene status, were collected. The efficacy and adverse events (AEs) occurring during ceritinib treatment were collected by means of outpatient and inpatient medical records, outpatient follow-up, and phone calls.
Inclusion and exclusion criteria
The inclusion criteria were as follows: (1) NSCLC diagnosed histopathologically or cytologically; (2) complete clinical staging according to the 8th edition of the AJCC staging system; (3) an ALK rearrangement detected by reverse transcription-polymerase chain reaction (RT-PCR), Ventana immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), or next-generation sequencing (NGS); (4) having received at least one dose (450 mg) of ceritinib under fed condition; and (5) complete medical records.
The exclusion criteria were as follows: (1) having received ceritinib targeted therapy and any other systemic antitumor therapy simultaneously or (2) follow-up could not be completed safely.
Efficacy evaluation
All patient data were collected by means of electronic medical records, phone calls, and outpatient follow-up. Whole-body efficacy was defined as the proportion of patients with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed using RECIST 1.1 (version 1.1 of the Response Evaluation Criteria in Solid Tumors) by the investigator. The evaluation of intracranial efficacy was divided into CR, PR, stable disease (SD), and progressive disease (PD) based on the Response Assessment in Neuro-Oncology (RANO) working group criteria. Objective response rate (ORR) was calculated by (CR + PR)/total cases × 100%, and disease control rate (DCR) was calculated by (CR + PR + SD)/total cases × 100%. Inspection methods included enhanced chest CT, enhanced whole abdomen CT, enhanced head MRI, whole-body bone scan, and PET/CT. The last follow-up was on May 15, 2020.
Statistical analysis
Frequency (%) and median (interquartile range) were used to describe the qualitative and quantitative data, respectively. A Chi-square test or Fisher's exact test was used to compare the ORR and DCR between patients with different characteristics. Kaplan–Meier method was used to estimate the survival curve, median progression-free survival (PFS), and 6- and 12-month event-free probabilities. The normal approximation method for the difference between two proportions was used to compare the estimated 6- and 12-month event-free probabilities between patients with different characteristics. R-3.6.2 software was used for data analysis.
| > Results | | |
Patient baseline
In total, 57 (26 males and 31 females) ALK-rearrangement NSCLC patients with BM were enrolled in this study with a median age of 50.0 years (range: 44.0–57.0 years). The number of patients with an ECOG PS score of 1, 2, 3, and 4 was 26, 17, 8, and 6, respectively. Four patients (including two cases of secondary malignant bone tumor, one case of secondary adrenal tumor, and one case of secondary high-grade neuroendocrine tumor) had a family history of tumors, one whose father suffered from lung cancer. Seventeen patients had a history of smoking, and all patients presented with stage IV lung adenocarcinoma. All patients were diagnosed with ALK rearrangement by FDA-approved tests. A variety of methods for detecting ALK rearrangements were performed in this group, including IHC in 30 cases, NGS in 17 cases, RT-PCR in seven cases, and FISH in three cases. ALK plus V-raf murine sarcoma viral oncogene homolog B1 (BRAF) was detected in one case. Two patients developed intracranial plus meningeal metastases, and 13 patients developed liver metastases. Fifty-three patients had received prior crizotinib, and one patient had received prior alectinib. Twenty-one patients had received at least one cycle of platinum-based doublet chemotherapy after experiencing disease progression during first-line TKI therapy. Moreover, 24 patients had received brain radiotherapy, and five patients underwent intracranial lesion resection. Ceritinib was administered to 21 patients in the first- or second-line setting and 36 patients in the third-, fourth-, or fifth-line setting. The last follow-up was on May 15, 2020. The average duration of ceritinib exposure was 9.38 months [Table 1].
Intracranial and whole-body efficacy analysis
By the end of the last follow-up, intracranial efficacy evaluation in 57 patients revealed that the best response to ceritinib was a CR in one patient, PR in 41 patients, SD in 11 patients, and PD in four patients [Supplementary Table 1]. The intracranial ORR and DCR were 73.7% (95% CI: 62.3–85.1) and 93.0% (95% CI: 86.3–99.6), respectively. Comparative analyses were done in the various subgroups (gender, smoking, chemotherapy, brain radiotherapy, ceritinib treatment line, and prior TKI), and the results indicated no statistical differences. With respect to whole-body efficacy evaluation, the best response to ceritinib was a CR in one patient, PR in 49 patients, SD in six patients, and PD in one patient [Supplementary Table 1]. The whole-body ORR and DCR were 87.7% (95% CI: 79.2–96.2) and 98.2% (95% CI: 94.8–100.0), respectively. Comparative analysis of the various subgroups revealed that the ORR of patients with prior brain radiotherapy was relatively higher compared with those who had not received prior brain radiotherapy (P = 0.044) [Table 2].
In addition, an analysis of the intracranial and whole-body PFS data was performed for this group. By the end of the last follow-up, 15 patients had an intracranial PFS, and 12 patients had a whole-body PFS, thus reaching the endpoint. Of these patients, the median intracranial PFS was 8.75 months (95% CI: 6.4–12.9), and the median whole-body PFS was 7.6 months (95% CI: 6.1–NE) [Figure 1]. Although the median intracranial PFS and median whole-body PFS for all patients were not reached [Figure 2], the prediction results suggested that the median intracranial PFS (95% CI: 12.9–NE) and the median whole-body PFS (95% CI: 15.2–NE) were non-evaluable. Therefore, we estimated the 6- and 12-month event-free probability for all patients. The estimated 6- and 12-month event-free probabilities for the intracranial lesions were 94.1% (95% CI: 87.8–100.1) and 68.1% (95% CI: 54.1–85.7), respectively, and those for the whole-body lesions were 94.1% (95% CI: 87.9–100.1) and 74.7% (95% CI: 61.8–90.3), respectively. Further subgroup analysis revealed that the estimated 12-month event-free probability for the intracranial lesions was relatively higher in patients with prior brain radiotherapy (93.8% vs. 47.1%, P = 0.0006) [Table 3] and [Supplementary Table 1]. | Figure 1: Survival Curve Based on the Median PFS of Patients Reaching the Endpoint. Of the patients who reached the endpoint, the median intracranial PFS was 8.75 months (95% CI: 6.4–12.9), whereas the median whole-body PFS was 7.6 months (95% CI: 6.1–NE)
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 | Figure 2: Survival Curve Based on the Median PFS of All Patients. The prediction results suggest the median intracranial PFS was non-evaluable (95% CI: 12.9–NE), and the median whole-body PFS was non-evaluable (95% CI: 15.2–NE)
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 | Table 3: Estimated 6- and 12-month Event-free Probabilities in Terms of Intracranial and Whole-Body Lesions
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Side effects
Of the 57 patients, 77.2% exhibited adverse drug reactions, and the most common AEs were diarrhea (11, 19.3%), nausea (6, 10.5%), vomiting (6, 10.5%), and anorexia (5, 8.8%). ALT was increased in three patients, whereas AST was increased in one patient. Of these patients, one suffered from vomiting caused by intolerance (AE grade 2) 3 months after receiving ceritinib at a dose of 450 mg QD under fed condition; therefore, the dose was reduced to 300 mg QD by the clinician after evaluation. Another patient suffered from severe diarrhea (AE grade 3) 3 months after receiving ceritinib under the same treatment conditions, and the dose was reduced to 300 mg QD by the clinician after evaluation, followed by 150 mg QD to ensure tolerability. The side effects from all the other patients were grade 1 or below, including transient discomfort, which was tolerated and did not require special treatment [Table 4].
Case
A 74-year-old female patient was admitted to the hospital because of “dyspnea for more than 2 months.” After admission, a contrast-enhanced CT of the chest revealed a 40 mm × 28 mm lobulated mass in the right lower lobe, pleural thickening, irregular enhancement after contrast injection, enlarged right hilar lymph nodes, and slightly increased bilateral axillary lymph nodes, indicating a high possibility of lung cancer with hilar lymph node metastases. On March 29, 2017, the patient underwent “video-assisted thoracoscopic right lower lobectomy, systematic lymph node dissection, and pleural adhesion cauterization.” Postoperative pathologic examination showed that the right lower lobe exhibited poorly differentiated adenocarcinoma (micropapillary component + solid component), which invaded the pleura. Immunohistochemical analysis of the adenocarcinoma components revealed ALK-V (+), ROS-1 (-), PDL1 (+, 10%), TTF-1 (+). Beginning from May 6, 2017, four cycles of AC chemotherapy (propranolol 750 mg + nedaplatin 100 mg) and 25 sessions of radiotherapy were completed. On May 15, 2018, a chest CT revealed lung cancer recurrence with double pulmonary metastases. Crizotinib was administered orally for more than 10 months. Dizziness, fatigue, and discomfort occurred during the treatment. On April 18, 2019, the patient developed a headache. An MRI of the head revealed multiple intracranial metastases. Crizotinib was stopped, and ceritinib was administered at a dose of 450 mg QD under fed condition for more than 3 months. The headache was relieved during treatment. A subsequent head MRI showed that the multiple intracranial metastases were smaller than that observed previously. The efficacy was evaluated as a PR. Because of intolerable diarrhea (AE grade 3), the dose was reduced to 300 mg QD. Diarrhea and discomfort (AE grade 2) occurred over the next 2 months, and the dose was further reduced to 150 mg QD for 7.5 months. Another head MRI showed that the multiple intracranial metastases continued to shrink, and the headache disappeared. The efficacy was evaluated as a PR. Blood abnormalities during treatment included alanine aminotransferase (ALT, 128 IU/L), aspartate aminotransferase (AST, 87 IU/L), and serum carbohydrate antigen 125 (CA125, 81.16 U/ml) [Figure 3]. | Figure 3: Changes in Patient Brain MRI Images. A 74-year-old female patient presented with ALK rearrangement and intracranial metastasis. The patient was administered a reduced dose of ceritinib to 150 mg QD (from April 23, 2019) because of intolerable side effects. After treatment for 7.5 months, she still exhibited continuous remission of intracranial lesions and an intracranial PFS of 12.9 months
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| > Discussion | | |
In China, ceritinib has been on the market for over 2 years. However, this study is the first to report preliminary efficacy data for ceritinib administered at a dose of 450 mg QD under fed condition for the treatment of ALK-rearrangement NSCLC patients with intracranial metastases in China.
By the end of the last follow-up, based on the observed efficacy statistics of ceritinib (450 mg QD under fed condition) for the treatment of intracranial metastases, the intracranial ORR was 73.7% (95% CI: 62.3–85.1), and the intracranial DCR was 93.0% (95% CI: 86.3–99.6), which are better than those of the ASCEND-7 study (ORR: 73.7% vs. 51.5% and DCR: 93.0% vs. 85.7%). The ASCEND-7 is the only study that evaluated the efficacy and safety of ceritinib (750 mg QD under fasted condition) for the treatment of advanced ALK-rearrangement NSCLC with brain and/or leptomeninges metastasis.[16] The reason why our data was better compared with that of the ASCEND-7 study may be that the ASCEND-7 study included patients with active brain metastases, which may result in a poor prognosis.[19] In addition, our real-world data showed that the estimated 6- and 12-month event-free probabilities of intracranial lesions were 94.1% (95% CI: 87.8–100.1) and 68.1% (95% CI: 54.1–85.7), respectively. Through subgroup analysis, we found that the estimated 12-month event-free probability of intracranial lesions was relatively higher in patients with prior brain radiotherapy (93.8% vs. 47.1%, P = 0.0006). The results from ASCEND-4 also showed that patients who had received brain radiotherapy exhibited a higher objective intracranial response rate compared with those who had not received radiotherapy.[10] By the end of the last follow-up, 15 patients had an intracranial PFS, reaching the endpoint, of which the median intracranial PFS was 8.75 months. Although the median intracranial PFS for all patients was not reached, the prediction results suggested the median intracranial PFS was non-evaluable (95% CI: 12.9–NE). Although the above data have never been reported, they show that ceritinib has promising intracranial antitumor activity in ALK-rearrangement NSCLC patients, similar to that reported in previous studies.[6],[7] Furthermore, with respect to whole-body efficacy evaluation, the ORR and DCR obtained in this study were 87.7% (95% CI: 79.2–96.2) and 98.2% (95% CI: 94.8–100.0), respectively. The preliminary efficacy data in this study are superior to that of the ASCEND-2 study (ORR: 87.7% vs. 38.6% and DCR: 98.2% vs. 77.1%).[8] Compared with the Japanese patient subgroup analysis in the ASCEND-5 study,[20] our study obtained a superior DCR (98.2% vs. 90.9%). According to the ASCEND-7 study, the estimated 6-month event-free probability of whole-body lesions reached 100% (the highest) in the subgroup of prior brain radiotherapy and no prior TKI (arm 3), and 64.4% (the lowest) in the subgroup of prior brain radiotherapy and prior TKI (arm 1). The estimated 12-month event-free probability of whole-body lesions reached 77.9% (the highest) in the subgroup of no prior brain radiotherapy and no prior TKI (arm 4), and 67.4% (the lowest) in the subgroup of prior brain radiotherapy and prior TKI (arm 1).[16] However, the 6- and 12-month event-free probabilities of whole-body lesions estimated in this study were 94.1% (95% CI: 87.9–100.1) and 74.7% (95% CI: 61.8–90.3), respectively. As per our subgroup analysis, the estimated 6-month event-free probability of whole-body lesions reached 100.0% (the highest) in the subgroup of prior brain radiotherapy and no prior TKI, and 66.7% (the lowest) in the subgroup of no prior brain radiotherapy and no prior TKI. The estimated 12-month event-free probability of whole-body lesions reached 93.9% (the highest) in the subgroup of prior brain radiotherapy and prior TKI and 64.2% (the lowest) in the subgroup of no prior brain radiotherapy and prior TKI. The ORR, DCR, and estimated event-free probability of our real-world data are superior to that of previous studies in terms of whole-body efficacy. By the end of the last follow-up in this study, 12 patients exhibited a whole-body PFS, reaching the endpoint, of which the median whole-body PFS was 7.6 months. Although the median whole-body PFS for all patients was not reached (95% CI: 15.2–NE), the prediction results suggested that it may be longer than the 7.9 months observed in the ASCEND-7 study. However, because of the small sample size and short follow-up duration of this study, efficacy data should be collected continuously in subsequent follow-ups. In addition, we presented the case of a 74-year-old female patient with an ALK rearrangement and intracranial metastasis. This patient received a reduced dose of ceritinib to 150 mg QD because of intolerable side effects. After treatment for 7.5 months, she still exhibited continuous remission of intracranial lesions, and the intracranial PFS was 12.9 months. The IC50 of ceritinib is the lowest compared with other ALK-TKIs.[21] We postulated that despite the low concentration of cerebrospinal fluid in ceritinib, it showed good intracranial control even when the dose was reduced to 150 mg QD.
In terms of AEs, we previously examined the safety of ceritinib (450 mg QD under fed condition) for the treatment of ALK-rearrangement NSCLC patients in China, in which a total of 109 patients were enrolled.[22] The incidence rates of all AEs and grade 3–4 AEs were 89.9% and 22.9%, respectively. The most common AEs (mainly in grades 1–2) were diarrhea (60.6%) and high ALT (38.5%) and AST (37.6%) levels in our previous study. For patients with BM, we found that 77.2% developed AEs, and the most common AEs included diarrhea (19.3%), nausea (10.5%), vomiting (10.5%), and anorexia (8.8%). Furthermore, ALT was increased in three patients, whereas AST was increased in one patient. The incidence rates in this study were generally lower than those observed in the previous study; however, both suggest the safety of ceritinib at 450 mg QD under fed condition is tolerable.
| > Conclusion | | |
According to our real-world data, ceritinib administered at a dose of 450 mg QD under fed condition to ALK-rearrangement NSCLC patients with BM in China exhibited superior ORR and DCR, as well as PFS and event free probability. In particular, for patients with prior brain radiotherapy, the estimated 12-month event-free probability of intracranial lesions and the whole-body ORR improved.
Abbreviations
QD: Quaque die/once a day
ALK: Anaplastic lymphoma kinase
NSCLC: Non-small cell lung cancer
ORR: Objective response rate
DCR: Disease control rate
RANO: Response Assessment in Neuro-Oncology
PFS: Progression-free survival
AEs: Adverse events
BM: Brain metastases
NE: Not evaluable
EFP: Event-free probability
TKI: Tyrosine kinase inhibitor
GI: Gastrointestinal
RT-PCR: Reverse transcription-polymerase chain reaction
IHC: Immunohistochemistry
FISH: Fluorescence in-situ hybridization
NGS: Next-generation sequencing
RECIST: Response Evaluation Criteria in Solid Tumors
CR: Complete response
PR: Partial response
SD: Stable disease
PD: Progression disease
ALT: Alanine aminotransferase
AST: Aspartate aminotransferase
CA: Carbohydrate antigen
CI: Confidence interval
BRAF: V-raf murine sarcoma viral oncogene homolog B1
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
This work was supported by the National Natural Science Foundation of China (CN) (81700095, 81870034), Central Guide Place-Free Exploration Project, Sichuan Provincial Department of Science and Technology (2020ZYD005), Science and Technology Plan Project (2019YFS0335).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]
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