Cetuximab Benefits Select Patients With Advanced Lung Cancer

Roxanne Nelson, RN, BSN

September 16, 2015

DENVER — The addition of cetuximab (Erbitux, Bristol Myers Squibb) to standard chemotherapy failed to improve survival in patients with advanced non-small-cell lung cancer (NSCLC), according to results from the large phase 3 SWOG S0819 trial.

However, certain subgroups of patients might derive a survival benefit.

The data indicate some increase in survival, although not significant, in patients who test positive for EGFR gene copy numbers with fluorescent in situ hybridization (FISH), regardless of tumor histology.

And in FISH-positive patients who did not receive bevacizumab (Avastin, Genentech), the increase in survival was significant; this was particularly pronounced in patients with squamous cell carcinoma.

In fact, for patients with FISH-positive squamous cell tumors, median overall survival was almost twice as long in those treated with cetuximab as in those treated with chemotherapy alone (11.8 vs 6.4 months, P = .006).

"Our hypothesis was that patients who had more than four copies of the EGFR gene were more likely to benefit from this therapy," said lead author Roy S. Herbst, MD, PhD, Ensign Professor of medicine and chief of medical oncology at the Yale Comprehensive Cancer Center in New Haven, Connecticut.

He presented the study results during the presidential session here at the 16th World Conference on Lung Cancer.

"If you look at the study as a whole, with all 1300-plus patients, there was no benefit to adding cetuximab to chemotherapy in either overall survival or progression-free survival," he reported.

These results were not a complete surprise. "If you don't select the right patients, this is probably not a therapy you should give," he said. "But for the 400 patients who were positive for this biomarker, we did see some signs of life."

For the 199 FISH-positive patients, median overall survival was better for those who received cetuximab than for those who did not (13.4 vs 9.8 months; hazard ratio [HR], 0.83, P = .10).

Prolonged Survival in Subgroups

The SWOG S0819 trial — launched in 2009 and conducted at more than 700 centers — involved 1313 patients with newly diagnosed stage IV NSCLC. The primary objective was to determine whether the addition of cetuximab to chemotherapy would benefit either unselected patients or those with specific biomarkers.

All 1313 patients received carboplatin and paclitaxel. Of these, 656 were randomized to receive concurrent cetuximab, and the remaining 657 served as the control group. Slightly more than half the patients did not meet the bevacizumab safety criteria for hemorrhage risk — 57% in the cetuximab group and 58% in the control group.

The primary end points were overall survival in the cohort as a whole and progression-free survival in the FISH-positive group. Secondary end points included the association between survival (overall and progression-free) and whether or not patients met the criteria for bevacizumab. An exploratory end point was overall survival in FISH-positive patients with squamous cell cancer.

The patients were stratified by bevacizumab criteria, smoking status, and disease substage (M1a or M1b).

For the cohort as a whole, cetuximab did not confer a significant benefit for progression-free survival (HR, 0.98; 95% confidence interval [CI], 0.87 - 1.09) or overall survival (HR, 0.94; 95% CI, 0.84 - 1.06).

For FISH-positive patients, there was a modest but nonsignificant improvement in progression-free survival (HR, 0.91; 95% CI, 0.71 - 1.12) and overall survival (HR, 0.83; 95% CI, 0.67 - 1.04).

But cetuximab significantly improved overall survival in FISH-positive patients who did not meet the criteria for bevacizumab (HR, 0.75; 95% CI, 0.57 -1.00; P = .048) and in patients with squamous cell carcinoma (HR, 0.56; 95% CI, 0.37 - 0.84; P = .048).

"Squamous cell lung cancer is a very difficult disease to treat, and there have been very few drugs for this group in the last decade," said Dr Herbst. "Here you can see a very significant result."

"This was the most compelling finding of the study," he pointed out.

Adverse event rates were similar in the two groups, and were consistent with those previously reported.

Patients Deserve Access to Therapies

EGFR-positivity indicated a "trend toward improved survival" in the cohort that received cetuximab, and it "increased survival in patients with squamous cell NSCLC," noted Robert Pirker, MD, professor of medicine and program director for lung cancer in the Department of Medicine I at the Medical University of Vienna.

He pointed out that in the SQUIRE trial, FISH-positivity enhanced the benefit of the investigational EGFR antibody necitumumab (Lilly).

"Chemotherapy plus cetuximab is a treatment option for patients with a high EGFR H score and FISH-positive squamous cell NSCLC," Dr Pirker explained. And "cisplatin and gemcitabine plus necitumumab is a treatment option for patients with squamous NSCLC — in particular, those with FISH-positivity or a high EGFR score."

Most important, he emphasized, "patients with advanced NSCLC deserve access to these therapeutic advances."

"Our purpose is not to do research for the sake of research, we also have to implement it in the clinic," Dr Pirker said. "Continuous research of bench to bedside and back does improve the care of patients with lung cancer."

The study was funded by the Southwest Oncology Group and the National Cancer Institute. Dr Herbst reports relationships with Biothera, Diatech, Kolltan, N of 1, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, and Pfizer. Dr Pirker reports relationships with AstraZeneca, MSD, Synta, Boehringer Ingelheim, Pfizer, Eil Lilly, and Pierrie Fabre.

16th World Conference on Lung Cancer (WCLC): Abstract Plen4.01. Presented September 9, 2015.

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