The idea of adding the targeted EGFR inhibitor cetuximab(Drug information on cetuximab) (Erbitux) to standard chemotherapy took a hit, as results from the SELECT phase III trial showed no improvement in efficacy when cetuximab was combined with pemetrexed(Drug information on pemetrexed) in patients with recurrent or progressive non–small-cell lung cancer (NSCLC).
Investigators led by Edward S. Kim, MD, of MD Anderson Cancer Center in Houston, initiated the SELECT trial after earlier, phase II studies showed that cetuximab improved response rates when added to chemotherapy regimens for patients with recurrent or progressive NSCLC. In a patient population of over 600, though, the hazard ratio for progression-free survival with cetuximab combined with pemetrexed vs pemetrexed alone was 1.0254 (P = .7560), indicating no benefit at all for the combination therapy. The overall survival results were similar, with an HR of 1.0148 (P = .8636).
The trial actually enrolled 938 patients with recurrent advanced NSCLC; physicians initially chose pemetrexed or docetaxel(Drug information on docetaxel) for patients, after which patients were randomized to either chemotherapy alone or in addition to a cetuximab regimen. The cetuximab combined with pemetrexed group ended up with 301 patients, 57.5% of whom were male; the average age was 62.8 years. In the pemetrexed alone group, there were 304 patients, 61.8% of whom were male, and the average age was 64 years. The two groups were well matched, though there was a trend toward more non–squamous-cell diagnoses in the pemetrexed alone group (P = .0555).
“We did not see any complete responses in this study of over 900 patients,” Dr. Kim said.
The overall response rate was 6.6% in the combination therapy group and 4.3% in the pemetrexed alone group (P = .2000). As Dr. Kim noted, all responses seen were partial responses, and disease control rates were similar between the two groups (52.2% combination vs 48.0% pemetrexed alone, P = .3097).
Most grade 3 or higher adverse events occurred at similar rates between the two groups, though 10.6% of cetuximab-treated patients had grade 3 or higher rash acneiform, compared with none in the pemetrexed alone group (P < .0001).
The investigators also examined whether EGFR status affected response to the study drugs, but there appeared to be no difference between EGFR-positive and other patients. Benjamin Solomon, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, said the null results of this study are quite clear, but there remains no obvious way to choose which patients should receive cetuximab.
“The study was very clear, there was no benefit seen, and no excuses found either: there was no benefit in nonsquamous patients and no benefit in EGFR-expressing patients,” Dr. Solomon said. He added that further molecular analyses from this study that could indicate a group of patients most likely to benefit are eagerly awaited.