Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr 27;2(1):e000168.
doi: 10.1136/esmoopen-2017-000168. eCollection 2017.

Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma

Vijay Maruti Patil  1 , Vanita Noronha  1 , Amit Joshi  1 , Anuradha Bharat Choughule  2 , Atanu Bhattacharjee  3 , Rajiv Kumar  4 , Supriya Goud  1 , Sucheta More  1 , Anant Ramaswamy  5 , Ashay Karpe  1 , Nikhil Pande  5 , Arun Chandrasekharan  1 , Alok Goel  1 , Vikas Talreja  1 , Abhishek Mahajan  6 , Amit Janu  1 , Nilendu Purandare  1 , Kumar Prabhash  1
Affiliations

Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma

Vijay Maruti Patil et al. ESMO Open. .

Abstract

Objective: Oral tyrosine kinase inhibitor has been shown to prolong progression-free survival (PFS) in estimated glomerular filtration rate (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.

Keywords: EGFR mutation; Gefitinib; Lung cancer; NSCLC; Palliative; Pemetrexed.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Progression free survival curve.
Figure 3
Figure 3
Forest plot for progression-free survival. Value below 1 suggests benefit from gefitinib. ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor.
Figure 4
Figure 4
Forest plot for overall survival. Value below 1 suggest benefit from gefitinib.
See this image and copyright information in PMC

References

    1. Pao W, Chmielecki J, Rational CJ. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer 2010;10:760–74. 10.1038/nrc2947 - DOI - PMC - PubMed
    1. Takeda M, Okamoto I, Nakagawa K. Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer 2015;88:74–9. 10.1016/j.lungcan.2015.01.026 - DOI - PubMed
    1. Rosell R, Carcereny E, Gervais R, et al. ; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239–46. 10.1016/S1470-2045(11)70393-X - DOI - PubMed
    1. 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 2011;12:735–42. 10.1016/S1470-2045(11)70184-X - DOI - PubMed
    1. Maemondo M, Inoue A, Kobayashi K, et al. ; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380–8. 10.1056/NEJMoa0909530 - DOI - PubMed