World Conference on Lung Cancer: Personalized Approaches to Treatment


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The 14th World Conference on Lung Cancer hosted more than 7,000 attendees in Amsterdam recently, with the theme “Better Care through Personalized Medical Approaches.” The following are brief summaries of key data presented at the conference, with perspective provided by Roy S. Herbst, MD, PhD, of Yale Cancer Center in New Haven, Connecticut (see sidebar on page 3).

First-line Erlotinib

In EURTAC (n = 174), the first phase III study of erlotinib (Tarceva) to include Western patients with non–small cell lung cancer (NSCLC) who had epidermal growth factors receptor (EGFR) mutations, first-line treatment with the drug nearly doubled progression-free survival compared with chemotherapy. Progression-free survival was 9.4 months vs 5.2 months, respectively, and median overall survival was 22.9 months and 18.8 months, respectively. Although 54.5% patients responded to erlotinib, the response rate was only 15.5% with chemotherapy, according to Gervais and colleagues from France.1

“We now have results for the use of first-line erlotinib in Asian and Western mutation-positive patients with NSCLC. I think EURTAC is a big step toward individualized lung cancer care,” said Radj Gervais, MD, of the Centre Francois Baclesse in Caen, France.

High EGFR Expression Predicts Survival

High levels of EGFR expression predicted prolonged survival in patients with NSCLC who received cetuximab (Erbitux) in combination with chemotherapy in the first-line setting, according to a new analysis of the phase III FLEX trial.2 Among 1,121 patients, researchers found that individuals with high EGFR expression (200+ on a scale of 0–300) consistently benefited from the addition of cetuximab. Their median overall survival was 12 months, compared with 9.6 months for the chemotherapy-alone arm, a 27% reduction in risk (P = .011). The 1-year survival rates were 50% vs 37%, and 2-year survival rates were 24% vs 15%, respectively. In patients with low EGFR expression, no overall survival difference was seen between the arms.

High EGFR expression is the first biomarker for overall survival in patients with advanced NSCLC who are treated with first-line chemotherapy combined with a targeted drug, noted Robert Pirker, MD, of the Medical University of Vienna.

EGFR Inhibitor Shows Promise

In a phase II trial of a pan-HER tyrosine kinase inhibitor that irreversibly binds to EGFR in patients previously treated with chemotherapy, PF-299804 produced superior progression-free survival: 12.4 months vs 8.3 months with erlotinib, a 34% reduction in risk (P = .012), plus a nonsignificant trend toward improved overall survival.3 On the basis of these positive results, Pfizer is conducting the phase III ARCHER trial, which will evaluate PF-299804 vs erlotinib.

ALK Rearrangement

ALK gene rearrangement was found in 9.6% of patients with lung cancer tested in the Lung Cancer Mutation Consortium and MET amplification was found  in another 4.1%, reflecting a subgroup of patients who might benefit from crizotinib.4 ALK mutations were associated with younger age, nonsmoking or never-smoking status, and presence of liver metastasis.

Crizotinib investigators reported overall survival data on 82 ALK-positive patients who received the novel drug vs matched historical controls.5 Median overall survival from the first-dose data has not been reached in the crizotinib group; 1‑year overall survival was 77%, and 2-year overall survival was 64%. Among controls, median overall survival was 20 months, while 1- and 2-year survival rates were 73% and 33%, respectively.

Response Predicted by PET

PET scanning with tracer [11C]erlotinib may provide a noninvasive method of identifying tumors that will respond to EGFR tyrosine kinase inhibitors. The study by Bahce et al6 included 10 NSCLC patients, 5 with wild-type EGFR and 5 with activating EGFR mutations who were scanned twice using a procedure that included a low-dose CT scan, a 10-minute [150]water dynamic PET scan, and a 1-hour [11C]erlotinib dynamic PET scan. Tumor uptake of [11C]erlotinib was significantly higher in the group with mutated EGFR than in the wild-type group (P = .03). Only tumors with high uptake of the tracer [11C]erlotinib responded to treatment with an EGFR inhibitor.

“This new imaging PET technique may be a noninvasive predictive marker that identifies NSCLC patients who benefit from treatment with tyrosine kinase inhibitors,” said Idris Bahce, MD, of VU University Medical Center in Amsterdam.

Endoscopy More Effective than Mediastinoscopy in Staging Lung Cancer

The ASTER study previously found that endosonography—combined endoscopic ultrasound/endobronchial ultrasound—followed by surgical staging when negative for malignancy, had significantly higher sensitivity and negative predictive value than surgical staging alone.7 Investigators reported that the strategy results in a cost savings ($1,210 per patient, $3,450 when mediastinoscopy is not required) and better quality of life.8 “Given that assessment of lymph glands using the endoscopic approach was more effective, better tolerated by patients, and no more expensive than the surgical approaches,” Robert Rintoul, MD, of the United Kingdom and his colleagues recommended this practice. ■

Disclosure: Dr. Pirker has received speaker’s fees and honoraria for serving on advisory boards from Merck Serono. Dr. Gervais reported no potential conflicts of interest. Dr. Rintoul’s institution, Papworth Hospital, Cambridge, UK, has received loan EBUS equipment and support for educational endosonography courses from Olympus UK

Expert Point of View: World Conference on Lung Cancer

References

1. Gervais R, Rosell R, Vergnenegre A, et al. 14th World Conference on Lung Cancer. Abstract 733. Presented July 4, 2011.

2. Pirker R, Paz Ares L, Eberhardt WEE, et al. 14th World Conference on Lung Cancer. Abstract 1557. Presented July 6, 2011.

3. Boyer M, Blackhall FH, Barrios CH, et al. 14th World Conference on Lung Cancer. Abstract 745. Presented July 4, 2011.

4. Vella-Garcia M, Iafrate JA, Pao W, et al. 14th World Conference on Lung Cancer. Abstract 1348. Presented July 5, 2011.

5. Shaw AT, Yeap B, Solomon B, et al. 14th World Conference on Lung Cancer. Abstract 1348. Presented July 6, 2011.

6. Bahce I, Lubberink M, Hendrikse NH, et al. 14th World Conference on Lung Cancer. Abstract 1910. Presented July 6, 2011.

7. Annema JT, van Meerbeeck JP, Rintoul RC, et al. JAMA 304:2245-2252, 2010.

8. Rintoul RC, Annema JT, Tournoy KG, et al. 14th World Conference on Lung Cancer. Abstract 840. Presented July 6, 2011.


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Roy S. Herbst, MD, PhDThe EURTAC study provides additional evidence of the efficacy of the oral EGFR inhibitors in the first-line treatment of patients with mutated EGFR—and, importantly, in Western patients, rather than Asians, for whom data are more abundant. “The findings speak to the fact that all patients with...


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