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Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma
  1. Vijay Maruti Patil1,
  2. Vanita Noronha1,
  3. Amit Joshi1,
  4. Anuradha Bharat Choughule2,
  5. Atanu Bhattacharjee3,
  6. Rajiv Kumar4,
  7. Supriya Goud1,
  8. Sucheta More1,
  9. Anant Ramaswamy5,
  10. Ashay Karpe1,
  11. Nikhil Pande5,
  12. Arun Chandrasekharan1,
  13. Alok Goel1,
  14. Vikas Talreja1,
  15. Abhishek Mahajan6,
  16. Amit Janu1,
  17. Nilendu Purandare1,
  18. Kumar Prabhash1
  1. 1Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
  2. 2Department of Molecular Biology Laboratory, Medical Oncology, Tata Memorial Hospital, Mumbai, India
  3. 3Department of Biometrics, Chiltern International Limited, Bengaluru, India
  4. 4Department of Pathology, Tata Memorial Hospital, Mumbai, India
  5. 5Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
  6. 6Departmet of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
  1. Correspondence to Dr Kumar Prabhash; kumarprabhashtmh{at}gmail.com

Abstract

Objective Oral tyrosine kinase inhibitor has been shown to prolong progression-free survival (PFS) in epidermal growthfactor receptor (EGFR) mutation positive adenocarcinoma; however, the comparator arm has not included the current standard adenocarcinoma regimen (pemetrexed carboplatin induction followed by maintenance pemetrexed) and patients from Indian subcontinent. Hence, this study was carried out in Indian patients to compare gefitinib with the above-mentioned chemotherapy regimen.

Methods This was an open-labelled, randomised, parallel group study comparing gefitinib (250 mg orally daily) with pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) doublet intravenous induction chemotherapy regimen followed by maintenance pemetrexed (500 mg/m2) in patients with EGFR-activating mutation-positive stage IIIB or stage IV adenocarcinoma lung in the first-line setting. The primary endpoint for the study was PFS. 260 patients were required to demonstrate a 50% improvement in PFS of gefitinib over chemotherapy, with 80% power and 5% type 1 error. With an expected 5% dropout rate, the sample size was 290 patients.

Results The median PFS in gefitinib arm was 8.4 months (95% CI 6.3 to 10.5 months) compared with 5.6 months (95% CI 4.2 to 7.0 months) in pemetrexed–carboplatin arm (HR: 95% CI 0.513 to 0.851; p −0.001). The impact of gefitinib on PFS was seen across all subgroups.There was no statistically significant difference in overall survival between the two arms. Haematologicalgrade3–4toxicities likeanaemia,neutropaenia and thrombocytopaenia were common in the pemetrexed–carboplatin arm while grade3–4 acneiform rash and diarrhoeawere common in the gefitinib arm.

Conclusion The study confirms the superiority of gefitinib in prolonging PFS against the most active chemotherapy regimen of pemetrexed–carboplatin followed by maintenance pemetrexed in EGFR-mutated lung adenocarcinoma. The median PFS in Indian patients in gefitinib arm is similar to that reported in east Asians and Caucasians.

  • EGFR mutation
  • NSCLC
  • Gefitinib
  • Pemetrexed
  • Lung cancer
  • Palliative

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors VP, KP : Concept, design, patient management, data entry, data analysis, data interpretation, first draft and final draft.

    VN : Concept, design, patient management, design entry, design analysis, data interpretation, first draft and final draft.

    AJ : Patient management, data interpretation, first draft and final draft.

    AC: Mutation analysis, first draft and final draft.

    AB : Statistical analysis, first draft and final draft.

    RV: Pathology reports,first draft and final draft.

    SG, SM : Patient management, first draft and final draft.

    AR, AK, NP, AC, AG, VT : Data entry, first draft and final draft.

    AM, AJ : Radiology, first draft and final draft.

    NP: Nuclear medicine, first draft and final draft.

  • Funding TRAC, intramural grant from Tata Memorial Hospital.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it was published Online First. Estimated glomerular filtration rate has been updated to read epidermal growth factor receptor.

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