January 04, 2017
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Platinum therapy superior in squamous NSCLC

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Platinum therapy appeared superior to nonplatinum chemotherapy for patients with non–small cell lung cancer with squamous histology, according to phase 3 study results.

“Most patients with advanced NSCLC are treated with a platinum doublet. An effective predictive biomarker is required to direct treatment to improve outcomes,” Siow Ming Lee, MD, PhD, professor of medical oncology at University College London and consultant medical oncologist at University College London Hospitals, and colleagues wrote. “ERCC1 gene polymorphisms have also been investigated, but results are inconsistent for NSCLC, again often on the basis of the retrospective studies.”

The phase 3 study included 648 patients with chemotherapy–naive stage IIB or stage IV NSCLC (squamous, n = 177; nonsquamous, n = 471).

Researchers randomly assigned patients with squamous disease to paclitaxel and gemcitabine or cisplatin and gemcitabine. Those with nonsquamous cancer received either cisplatin and pemetrexed or paclitaxel and pemetrexed.

OS served as primary outcome. Researchers also evaluated clone 3F2, an antibody specific for XPF. Lee and colleagues established a target HR of 0.78 or less for patients with ERCC1–positive NSCLC.

More than half of patients were ERCC1 positive in both the squamous (54.5%) and nonsquamous (76.7%) groups. Also, more than half of patients in the squamous (70.5%) and nonsquamous (68.5%) groups were XPF positive.

Researchers stopped accrual of patients with squamous disease in 2012 after platinum therapy showed a superior OS. Patients assigned paclitaxel and pemetrexed achieved median OS of 7.6 months, whereas those assigned cisplatin and gemcitabine achieved a median OS of 10.7 months (HR = 1.46; P = .02).

Accrual of patients with nosquamous disease stopped in 2013.

Among patients with ERCC1–positive disease, median OS was 8 months for those assigned paclitaxel and pemetrexed, compared with 9.6 months for those assigned cisplatin and pemetrexed (HR = 1.11; 95% CI, 0.85-1.44).

Among patients with ERCC1–negative disease, median OS was 10.3 months for those assigned paclitaxel and pemetrexed vs. 11.6 months for those assigned cisplatin and pemetrexed (HR = 0.99; 95% CI, 0.73-1.33).

Neither XPF nor ERCC1 were prognostic (positive vs. negative ERCC1, HR for OS = 1.11; positive vs. negative XPF, HR for OS = 1.08).

The “relatively low dose intensity might have influenced results,” Sophie Postel-Vinay, MD, PhD, and Jean-Charles Soria, MD, PhD, both of the drug development department at Gustave Roussy Cancer Campus at Parils-Saclay University, wrote in an accompanying editorial.

“Taken together, these elements support further assessment of ERCC1 as a predictive marker for platinum-based chemotherapy; however, the results also provide evidence to suggest that the tools to perform such an evaluation are not yet optimal,” Postel-Vinay and Soria wrote. “Far from throwing the baby out with the bathwater, the ERCC1 Trial results call for further investigations in the field of cytotoxic chemotherapy predictive biomarkers and highlight the considerable challenges still ahead.” – by Andy Polhamus

Disclosure: Lee reports consultant or advisory roles with Bristol-Myers Squibb and Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures. Postel-Vinay reports no relevant financial disclosures. Soria reports honoraria from Astex, AstraZeneca, Clovis, Eli Lilly, Genentech, GlaxoSmithKline, MedImmune, Merck Sharp & Dohme, Merus, Mission Therapeutics, MSD Oncology, Pfizer, Pharmamar, Pierre Fabre, Sanofi, Servier, Symphogen and Takeda, as well as patents or intellectual property related to use of ERCC1 to select chemotherapy in lung cancer.