Post-Resistance Gefitinib Fails to IMPRESS in Advanced NSCLC

Continuing gefitinib therapy after disease progression does not improve NSCLC survival

medwireNews: The IMPRESS trial has failed to show a significant benefit for continuing gefitinib therapy in non-small-cell lung cancer (NSCLC) patients who develop resistance after first-line treatment with the Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI).

Progression-free survival was a median of 5.4 months for both the 133 chemotherapy-naive patients with stage IIIB to IV NSCLC who were randomly assigned to continue gefitinib alongside cisplatin and pemetrexed chemotherapy and the 132 patients who were given placebo with their platinum-based doublet therapy.

After a median of 11.2 months, a comparable 74% of gefitinib- and 81% of placebo-treated patients experienced disease progression, report Tony Mok, from Prince of Wales Hospital in Hong Kong, China, and co-investigators.

The team had hypothesised that continuing gefitinib after disease progression might be beneficial as there are multiple causes of acquired resistance to EGFR TKIs and some sites of tumour metastases could continue to be sensitive to treatment.

But there was no significant difference in the proportion of gefitinib- and placebo-treated patients in the phase III trial who achieved an objective response (32 vs 34%) or disease control (84 vs 79%).

And overall survival data at the time of data cutoff were immature and inconclusive, but suggested a poorer outcome for gefitinib-treated patients, at a median of 14.8 versus 17.2 months.

The treatment groups also achieved comparable improvements in health-related quality of life and there was no significant difference in the time to worsening of these measures.

“Therefore, platinum-based doublet chemotherapy remains the standard of care in this setting”, the researchers summarise in The Lancet Oncology.

The team notes that gefitinib plus chemotherapy was “well tolerated”; severe adverse events were reported in 28% of gefitinib-treated patients and 21% of the placebo group, with 8% and 10% of patients discontinuing treatment, respectively.

Mok et al conclude: “[F]urther data for doublet chemotherapy in the second-line setting after progression on first-line EGFR TKI treatments are needed to confirm this finding, such as the ongoing phase 3 open-label AURA 3 study of AZD9291 versus platinum-based doublet chemotherapy in patients with EGFR-mutation-positive NSCLC (with tumours harbouring a T790M mutation) and experience of disease progression on previous EGFR TKI therapy.”

Reference

Soria J-C, Wu Y-L, Nakagawa K, et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol 2015; Advance online publication 6 July. DOI: dx.doi.org/10.1016/S1470-2045(15)00121-7

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