|Year : 2021 | Volume
| Issue : 3 | Page : 116-118
Indian subset analysis of a phase iiib open-label study of afatinib in epidermal growth factor receptor tyrosine kinase inhibitor-naïve patients with epidermal growth factor receptor mutation positive non-small cell lung cancer
Senthil J Rajappa1, BJ Srinivasa2, Shailesh A Bondarde3, Partha Mohan Gokhale4, Pankaj Sonone4, Arun Kumar Dahiya4
1 Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Medical Oncology, HCG Hospital, Bengaluru, Karnataka, India
3 Department of Medical Oncology, Shatabdi Superspeciality Hospital, Nashik, Maharashtra, India
4 Department of Medical Affairs, Boehringer Ingelheim India Pvt. Ltd., Mumbai, Maharashtra, India
|Date of Submission||20-Sep-2021|
|Date of Decision||30-Oct-2021|
|Date of Acceptance||22-Nov-2021|
|Date of Web Publication||14-Dec-2021|
Arun Kumar Dahiya
1102, Hallmark Business Plaza, Kala Nagar, Near Gurunanak Hospital, Bandra East, Mumbai - 400 051, Maharashtra
Source of Support: None, Conflict of Interest: None
Aims: The study aimed to evaluate the safety and efficacy of afatinib in locally advanced or metastatic nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, in Indian subset of a Phase IIIB open-label study. Methods: A multicenter, open-label, Phase IIIB study was conducted to evaluate afatinib in EGFR tyrosine kinase inhibitor-naïve patients with locally advanced/metastatic EGFRm + NSCLC across five countries (34 sites; China, Hong Kong, India, Singapore, and Taiwan). A total 541 patients were recruited, out of which 50 patients were from India. In this article, we have evaluated the safety and tolerability of afatinib in Indian subset of patients (n = 50). Treatment with afatinib was continued until lack of clinical benefit as determined by the investigator. Primary endpoint was safety in terms of patients with serious adverse events (SAEs). Secondary endpoints included number of patients with drug-related AEs, time to symptomatic progression (TTSP), and progression-free survival (PFS). Results: Forty-six out of 50 patients experienced at least one AE. As in the overall study, diarrhea was the most common drug-related AE in Indian patients. In majority (85%) of cases, severity of diarrhea was of grade 1 or 2. No new safety concern was identified in the study. Median TTSP and PFS were 13.43 months (95% confidence interval [CI]: 8.51, 18.33) and 10.08 months (95% CI: 7.32, 14.75), respectively, in Indian subset. Conclusions: Safety and tolerability of afatinib were consistent with overall study and previously reported data. Most of the AEs were manageable without any need of treatment discontinuation.
Keywords: Afatinib, epidermal growth factor receptor, nonsmall cell lung cancer, time to symptomatic progression, tyrosine kinase inhibitors
|How to cite this article:|
Rajappa SJ, Srinivasa B J, Bondarde SA, Gokhale PM, Sonone P, Dahiya AK. Indian subset analysis of a phase iiib open-label study of afatinib in epidermal growth factor receptor tyrosine kinase inhibitor-naïve patients with epidermal growth factor receptor mutation positive non-small cell lung cancer. Oncol J India 2021;5:116-8
|How to cite this URL:|
Rajappa SJ, Srinivasa B J, Bondarde SA, Gokhale PM, Sonone P, Dahiya AK. Indian subset analysis of a phase iiib open-label study of afatinib in epidermal growth factor receptor tyrosine kinase inhibitor-naïve patients with epidermal growth factor receptor mutation positive non-small cell lung cancer. Oncol J India [serial online] 2021 [cited 2022 Jan 21];5:116-8. Available from: https://www.ojionline.org/text.asp?2021/5/3/116/332511
| Introduction|| |
Afatinib, an orally administered irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated safety and efficacy in patients with EGFR mutation-positive (EGFRm+) nonsmall cell lung cancer (NSCLC) in several trials, namely phase III LUX-Lung 3 and 6 trials, and phase IIb LUX-Lung 7 trial.,, However, prospective Indian data supporting clinical benefit of afatinib in real-world settings is limited. Here, we report Indian subset analysis of a Phase IIIb, open-label, single-arm, multicenter study (www.clinicaltrials.gov: NCT01953913), to assess safety and efficacy of afatinib in EGFR TKI-naïve patients with locally advanced/metastatic EGFRm + NSCLC.
| Methods|| |
This study was conducted over a period from 2013 to 2018. EGFR TKI-naïve patients with locally advanced/metastatic EGFRm + NSCLC were recruited from 34 sites in China, Hong Kong, India, Singapore, and Taiwan. Patients received 40 mg/day afatinib. A dose reduction to a minimum of 20 mg/day was permitted. Treatment continued until lack of clinical benefit as determined by the investigator. The trial was approved by local independent ethics committee at every site. Primary endpoint was safety in terms of patients with serious adverse events (SAEs). Secondary (other safety and efficacy) endpoints included number of patients with drug-related AEs, time to symptomatic progression (TTSP), progression-free survival (PFS), objective response, and duration of disease control.
| Results|| |
Five hundred and forty-one patients were recruited in the global study, out of which approximately 10% (n = 50) were Indians. Data presented here are of all 50 Indian patients and are descriptive in nature. Twenty-nine patients had received chemotherapy before entering the study. At the time of screening, 12% patients had uncommon mutations, and 20% had brain metastasis. Detailed baseline characteristics are mentioned in [Table 1] and [Table 2].
Forty-six patients experienced at least one adverse event (AE), refer to [Table 3] for details. Diarrhea was the most common drug-related AE; however, in majority (85%) of cases, diarrhea severity was of grade 1 or 2. Twenty-two patients suffered SAEs, out of which seven had drug-related SAEs. The only drug-related SAE occurring in >1 patient was diarrhea (n = 3; two with grade 3 and one with grade <3). Nineteen patients required dose reduction due to “any AE,” diarrhea being the most common cause (n = 10). Two patients discontinued treatment because of drug-related AEs.
In Indian patients, median TTSP was 13.43 months (95% confidence interval [CI]: 8.51, 18.33) and median PFS was 10.08 months (95% CI: 7.32, 14.75) [Figure 1].
Objective responses were reported in 23 patients (46%) by week 96; the median duration of objective response was 12.94 months (95% CI: 9.62, 19.21). Forty (80%) patients achieved disease control, with median duration of 10.57 months (95% CI: 8.21, 15.76).
| Discussion|| |
Afatinib is an irreversible second-generation ErbB family blocker, approved in many countries for the treatment of advanced EGFR mutation-positive (EGFRm+) NSCLC in the first line. Data from two phase III clinical trials demonstrated favorable efficacy with afatinib compared to standard platinum-based chemotherapy., Afatinib also demonstrated significant efficacy compared to gefitinib, a first-generation reversible EGFR TKIs in a phase IIb trial.
An open-label, multicenter, single-arm trial was conducted to assess the safety of afatinib in 541 patients with locally advanced or metastatic NSCLC harboring EGFR mutation(s) out of which 50 patients were from India. Here, we have analyzed the safety and efficacy of afatinib in the Indian subset (n = 50). Most of the baseline characteristics were matching with the overall population included in the study except there were higher number of patients receiving afatinib in ≥2 line therapy in Indian subset.
In phase III clinical trial of afatinib, diarrhea was the most commonly reported AE with 14.4% patients' ≥ Grade 3. Similarly, in this study, the most commonly reported AE in the Indian subset as well as overall populations was diarrhea. The proportion of patients experiencing ≥ Grade 3 diarrhea in the Indian subset (12%) was similar to overall population. Other AEs reported in this study were rash, paronychia, stomatitis, and the overall safety profile of afatinib in Indian patients was consistent with the overall study population and no new safety signal were reported.
The efficacy endpoints analyzed in this study were median TTSP and PFS, which were 13.43 months (95% [CI]: 8.51, 18.33) and 10.08 months (95% CI: 7.32, 14.75), respectively. These results were consistent with the efficacy observed in the overall population; median TTSP of 14.0 months (95% [CI]: 12.9, 15.9) and median PFS of 12.1 months (95% CI: 11.0, 13.6). The overall efficacy of afatinib in Indian patients in this study was similar to the previous clinical trials; LUX-Lung 3 (median PFS 11.1 months) and LUX-Lung 6 (median PFS 11.0 months and median time-to-treatment failure of 13·7 months).,
| Conclusions|| |
The study adds to the data from randomized controlled trials on patients with EGFR + NSCLC. Safety and tolerability of afatinib were consistent with previously reported data. Most of the AEs were manageable and did not lead to treatment discontinuation. Furthermore, efficacy data were encouraging, median TTSP being more than 13 months.
The authors would like to acknowledge the assistance provided by Tuton Naik, Marketing manager, Oncology Division, Boehringer Ingelheim in interpretation of the data (when applicable) and preparation of the manuscript.
Financial support and sponsorship
Data analysis was supported by Boehringer Ingelheim India Pvt. Ltd.
Conflicts of interest
Dr. Arun Kumar Dahiya and Dr. Partha Gokhale are currently, and Dr. Pankaj Sonone was earlier, employed by Boehringer Ingelheim.
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[Table 1], [Table 2], [Table 3]