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First-line icotinib confers PFS advantage in EGFR-positive advanced lung adenocarcinoma

Jairia Dela Cruz
13 Sep 2017

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) icotinib affords improved progression-free survival (PFS) in the first line treatment of advanced lung adenocarcinoma patients bearing EGFR mutations, with a tolerable and manageable safety profile, as shown in the phase III CONVINCE trial.

Icotinib significantly prolonged the primary endpoint of PFS, as assessed by an independent response evaluation committee (IREC), compared with intravenous chemotherapy using cisplatin and pemetrexed (median, 11.2 vs 7.9 months; hazard ratio [HR], 0.61; 95 percent CI, 0.43 to 0.87; p=0.006). [Ann Oncol 2017;doi:10.1093/annonc/mdx359]

HRs for PFS favoured the icotinib arm across subgroups stratified by EGFR mutations (exon 19 Del and 21 L858R) and by clinical factors (Eastern Cooperative Oncology Group performance status, gender, smoking status, mutation type and disease stage).

On the other hand, no significant difference was seen in overall survival (OS) between the icotinib and chemotherapy arms. This was true in the overall population (median, 30.5 vs 32.1 months, respectively; p=0.8854) and in EGFR subgroups of 19 Del (median, 32.3 vs 38.8 months; p=0.4066) and 21 L858R (median, 29.1 vs 26.7 months; p=0.5259).

Icotinib demonstrated a safety profile consistent with that observed in previous studies, and no new safety signal was reported. Adverse events (AEs; 79.1 vs 94.2 percent; p<0.001) and treatment-related AEs (54.1 vs 90.5 percent; p<0.001) occurred with less frequency in the icotinib than in the chemotherapy arm.

The most common grade 3 or 4 AEs were rash (14.8 percent) and diarrhoea (7.4 percent) with icotinib vs nausea (45.9 percent), vomiting (29.2 percent) and neutropoenia (10.9 percent) with chemotherapy. AEs led to treatment discontinuation in three patients (2 percent) in the icotinib arm vs 24 (17.5 percent) in the chemotherapy arm.

A total of 285 patients with EGFR-positive advanced lung carcinoma patients comprised the study population, with 148 randomly treated with oral icotinib (125 mg, three times/day) and 137 with intravenous chemotherapy (75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed on day 1). Median duration of treatment was 10 months in the icotinib arm and 7 cycles in the chemotherapy arm.

“Icotinib has been previously shown to be noninferior to gefitinib in nonselected advanced nonsmall cell lung cancer patients when given as second- or further-line treatment,” the investigators said, adding that the present data provide the first direct evidence of superiority of icotinib over first-line cisplatin/pemetrexed plus pemetrexed maintenance in untreated patients with EGFR mutation-positive lung adenocarcinoma.

The investigators explained that the similar OS results could be attributed to the potential offsetting of the EGFR TKI benefit by subsequent treatments postprogression, “as 92.5 percent of the icotinib arm received further treatment with chemotherapy or other EGFR TKIs [whereas] 82.8 percent of the chemotherapy arm received poststudy EGFR TKIs.”

Despite the lack of rebiopsy for patients with progressive disease to assess mechanisms for resistance for icotinib, the current study suggests that icotinib should be considered as a standard first-line treatment option for advanced lung adenocarcinoma patients with EGFR mutations, according to the investigators.

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Most Read Articles
Audrey Abella, 09 Jun 2017
Maintenance therapy with olaparib significantly improved progression-free survival (PFS) and patient-centred benefits in patients with germline BRCA-mutated, platinum-sensitive relapsed serous ovarian cancer (gBRCAm PSR SOC) compared with placebo, according to the SOLO* 2 trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 held in Chicago, Illinois, US.
Elvira Manzano, 14 Jun 2017
The oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) in women with BRCA-positive, HER2-negative breast cancer compared with standard chemotherapy in the phase III OlympiAD* trial, ushering in a new era of hope in BRCA-mutated breast cancer.
Pearl Toh, 01 Aug 2016
Understanding biomarkers predictive of treatment outcomes or response can help inform treatment decisions and personalize care for advanced prostate cancer patients, suggested an expert at the recent Urological Association of Asia Annual Congress (UAA 2016) held in Singapore.
Audrey Abella, 13 Jun 2017
A psychological intervention, Conquer Fear, may help alleviate fear of cancer recurrence (FCR) in cancer survivors, according to a study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 held in Chicago, Illinois, US.