Lung Cancer: Poster Discussion Session and Oral Abstracts, Monday June 1st

Post by M. Catherine Pietanza, MD:

Once again, a common theme in the treatment of NSCLC was that molecular characterization is necessary and will assist in directing the appropriate therapies toward our patients.

Multiple presentations showed the ability of using molecular markers to guide patient selection for trials, of which I will provide a few examples. The North-East Japan Gefitinib Study Group presented phase III data where 198 patients with newly diagnosed, advanced NSCLC and EGFR activating mutations were randomized to receive either gefitinib or carboplatin/paclitaxel (Abstract #8016). The results of this trial are impressive and show that the response rates and median progression free survival for patients randomized to gefitinib compared to those receiving chemotherapy were 75% and 10.6 months versus 29% and 5.5 months, respectively. This study validates the use of EGFR tyrosine kinase inhibitors in the first line setting for patients with activating mutations. Several other studies based patient eligibility upon the presence of activating EGFR mutations (Abstracts #8013, #8023, #8026). In a phase II study using salirasib, which inhibits RAS binding to plasma membrane and blocks RAS-dependent cell growth, Johnson et al. demonstrated that K-RAS selective trials are feasible (Abstract #8012). These data underscore the importance of genotyping NSCLC, as has become a standard at our institution.

Two abstracts showed that biopsying patients upon progression of disease was safe and feasible. The BATTLE study presented by Kim et al. at MD Anderson Cancer Center demonstrated that rebiopsy allowed for the identification of biomarkers prospectively, the results of which directed patient treatment in various available protocols (Abstract #8024). Similarly, Dr. Arcila and colleagues at Memorial Sloan-Kettering Cancer Center showed that patients can be rebiopsied when they no longer respond to EGFR tyrosine kinase inhibitors to determine the patterns of resistance and guide decision making for further targeted therapies (Abstract #8025).

A few important points were garnered during the oral presentations focusing on local-regional and adjuvant treatment for NSLC. Updated survival analysis of JBR.10, the randomized phase III study comparing cisplatin/vinorelbine to observation in patients with resected stage IB and II was presented (Abstract #7501). After a median follow-up of greater than nine years, survival analysis continues to show a benefit for adjuvant chemotherapy (HR 0.78 with p = 0.04), which is primarily in patients with stage II disease. Adjuvant chemotherapy for patients with stage IB remains controversial, although there is a trend toward improved outcomes for those with large tumors. Importantly, in early stage disease, biomarkers also may be able to predict benefit from adjuvant chemotherapy, as demonstrated in the study presented by Dr. Fouret (Abstract #CRA7502). Here, tissue samples of patients that had participated in the IALT trial were studied in a retrospective manner and MSH2 was identified as a predictive marker. Further studies are warranted to prospectively analyze biomarkers, which are underway.

A phase II study comparing pemetrexed, carboplatin, and concurrent thoracic radiation with or without cetuximab (CALGB 30407) showed that this regimen is safe and effective, with both arms meeting a predefined threshold of median survival of 20.9 months (Abstract #7505). However, the addition of cetuximab did not benefit outcomes. Further, there was a trend toward better outcomes observed with non-squamous NSCLC. The results of this work are being used to launch two large phase III studies, one of which will contain a pemetrexed arm in non-squamous NSCLC and another will address the use of cetuximab. The RTOG 0214 study attempted to evaluate prophylactic cranial irradiation (PCI) in patients that had completed treatment for locally advanced disease (Abstract # 7506). The study did not meet its target accrual and closed early, thus was not able to show benefits in outcomes. It demonstrated that PCI decreased the incidence of CNS metastases in this group of patients. Quality of life data will be presented later in the year.

In small cell lung cancer, treatment options continue to be limited. Several abstracts showed that the standard of care for first line treatment of extensive stage SCLC remains etoposide/platinum in the US and Europe, whereas in Japan it is irinotecan/platinum (Abstracts #8027 and #8029). In the second-line setting, amrubicin was compared to topotecan in a randomized phase II trial for patients with relapsed sensitive SCLC and found to have significantly improved response rate and a trend toward improved survival (Abstract #8028). Similarly, amrubicin shows response in those patients with refractory disease (Abstract #8103).

This marks the end of the lung cancer presentations at ASCO 2009. I hope you found these summaries helpful.