ORLANDO, June 1 — A two-drug maintenance regimen delayed recurrence of advanced non-small cell lung cancer better than a single drug, a researcher said here.

• Explain to patients that therapy for advanced non-small cell lung cancer now may include the monoclonal antibody bevacizumab (Avastin), which is used during initial chemotherapy and as maintenance treatment after the chemo is finished.
• Note that this study examined the effect of adding a second drug to the maintenance regimen and found somewhat promising results.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The drugs — bevacizumab (Avastin) and erlotinib (Tarceva) — were compared to bevacizumab plus placebo after the completion of standard chemotherapy, according to Vincent Miller, M.D., of Memorial Sloan-Kettering Cancer Center in New York City.

The delay — while statistically significant at P=0.001 — was not startlingly large. Patients getting bevacizumab and placebo had a median progression-free survival of 3.75 months, compared with 4.76 for those getting both drugs. But the results were promising, he told colleagues at the American Society of Clinical Oncology meeting here.

Bevacizumab is already a major component of therapy for patients with advanced disease, Dr. Miller said.

The new findings come from the so-called ATLAS trial, which enrolled 1,160 patients with locally advanced, recurrent, or metastatic non-small cell lung cancer.

After four cycles of first-line chemotherapy (which included bevacizumab), the 769 patients who had not progressed were randomized to one of the two maintenance therapy regimens.

Analysis showed “we can delay progression with the addition of a targeted agent,” Dr. Miller said.

Although the delay itself was not long, Dr. Miller said median progression-free survival might not tell the whole story. He pointed to the hazard ratio for progression, which was 0.77 in favor of the pair of drugs. (95% CI 0.59 to 0.88.)

In addition, he said, the rate of progression-free survival at various times during treatment will be important.

For example, he said, at three months, 53.4% of single-drug patients were still free of disease, compared with 67.7% of those getting the two drugs.

At six months, the comparable figures were 28.4% and 40.3%, he said.

Dr. Miller said that, in the long run, the two-drug strategy might be reserved for subsets of patients.

“My general feeling is that the strategy will not be employed in all patients, but in perhaps in select patients, say, who remained symptomatic after their initial therapy,” he said.

One advantage of both drugs is that they can be used extensively without building up side effects, said Bruce Johnson, M.D., of the Dana-Farber Cancer Institute, who was not part of the study.

“By and large, you can give those drugs for months and sometimes even years without big increases in cumulative toxicity,” he said.

But before the two-drug combination is accepted, he said, he and others are likely to wait to see what effect — if any — it has on overall survival.

“If longer progression-free survival tracks with overall survival, the interest is higher,” he said.

The study was supported by Genentech, which markets Avastin and Tarceva. Dr. Miller and colleagues reported financial links with the company. Dr. Johnson reported financial links with Genzyme, Boston Scientific, Celgene, and Johnson and Johnson.

Primary source: Journal of Clinical Oncology

Source reference:

Miller VA, et al “A randomized, double blind, placebo controlled, Phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for 1st-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC)” J Clin Oncol 2009; 27(15S): Abstract LBA8002.

ORLANDO, June 1 — A DNA repair gene’s activity level predicts how well patients with non-small cell lung cancer will respond to some forms of chemotherapy, a French researcher said here.

• Explain to interested patients that treatment of early-stage non-small cell lung cancer with cisplatin-based chemotherapy after surgery has been shown to improve survival.
• Note that this study found that patients with low levels of two DNA repair genes were more likely to do well with this therapy.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Low activity of the gene MSH2 — originally associated with hereditary nonpolyposis colon cancer — indicates that patients will do better with cisplatin-based chemotherapy, according to Pierre Fouret, M.D., Ph.D., of Universite Pierre et Marie Curie in Paris.

The effect is similar to that already observed with another DNA repair gene, dubbed ERCC1, Dr. Fouret said at the annual meeting of the American Society of Clinical Oncology.

The finding could be used to personalize cancer care for patients with the disease, Dr. Fouret said, sparing some from useless therapy.

The MSH2 gene has a contradictory effect, according to George Simon, M.D., of Fox Chase Cancer Center in Philadelphia, who was not part of the research but who has studied the issue.

On one hand, the gene’s ability to repair DNA means that tumors with high levels of the protein tend to have cells more like normal cells and are therefore less aggressive.

But that same capacity means these tumors are more resistant to cisplatin-based chemotherapy, which relies on disrupting the DNA of cancer cells.

Dr. Fouret said the new finding comes from the International Adjuvant Lung Trial, which tested whether cisplatin-based chemotherapy or observation was a better strategy in early stage cancer that could be completely removed surgically.

In the overall trial, researchers concluded that the chemotherapy improved survival, but not all patients benefited, according to Dr. Fouret. In an effort to find out why, they studied tissue samples from 673 evaluable tumors.

He and colleagues correlated levels of MSH2 with survival results from the original trial and found that low levels of the protein were associated with a better outcome after chemotherapy.

Specifically:

• 38% of the tumors were MSH2 positive and 62% were MSH2 negative.
• Chemotherapy prolonged survival in the MSH2 negative group, with an adjusted hazard ratio for death, compared with observation, of 0.76 (95% CI 0.59 to 0.97 P=0.03).
• In the MSH2 positive group, the adjusted hazard ratio for death was 1.12, which was not significant.
• Among patients in the control arm, the hazard ratio for death associated with MSH2 positivity, compared with negativity, was 0.66 (95% CI 0.49 to 0.90, P=0.01).

Dr. Simon said the latter finding reflects the relatively beneficial effect of the gene when the tumors are simply left alone.

Dr. Fouret said the researchers also looked at the effect of ERCC1, both alone and in combination with MSH2, and found that when the two genes were both at low levels, there was a 35% reduction in the risk of death in the chemotherapy arm.

The utility of the finding may simply be to spare some patients — those who are not likely to benefit — from the rigors of the cisplatin-based chemotherapy, Dr. Simon said.

If such patients such patients get the therapy, he said, “all you give them is side effects.”

The study was supported by the Institut Gustave-Roussy, the Programme Hospitalier de Recherche Clinique, the Ligue Nationale Contre le Cancer, sanofi-aventis, and Pierre Fabre Oncology. Dr. Fouret said he had no disclosures to report. Dr. Simon said he had no disclosures to report.

Primary source: American Society of Clinical Oncology

Source reference:

Fouret P, et al “MSH2 and adjuvant cisplatin-based chemotherapy in non-small-cell lung cancer” ASCO 2009; Abstract CRA7502.

CHICAGO, June 1 — Negative top-line findings from a large Norwegian study of flexible sigmoidoscopy for colorectal cancer screening don’t necessarily mean the procedure is ineffective, two colorectal cancer experts agreed in this exclusive MedPage Today Infocus discussion.

Dissecting the randomized, 55,000-patient NORCCAP trial, reported here at Digestive Disease Week and published in an early online release by BMJ, were Marcia Cruz-Correa, M.D., of the University of Puerto Rico in San Juan, and Douglas Rex, M.D., of Indiana University Medical Center in Indianapolis.

They said additional follow-up in the study — planned to continue for another eight years — would give a better picture of the utility of flexible sigmoidoscopy and its optimal place in U.S. practice.