Summary Statement Novel Agents in the Treatment of Lung Cancer: Fifth Cambridge Conference Assessing Opportunities for Combination Therapy

The promise of effective targeted therapy for lung cancer requires rigorous identification of potential targets combined with intensive discovery and development efforts aimed at developing effective "drugs" for these targets. We now recognize that getting the right drug to the right target in the right patient is more complicated than one could have imagined a decade ago. As knowledge of targets and development of agents have proliferated and advanced, so too have data demonstrating the biologic heterogeneity of tumors. The finding that lung cancers are genetically diverse and can exhibit several pathways of resistance in response to targeted agents makes the prospect for curative therapy more daunting. It is becoming increasingly clear that single-agent treatment will be the exception rather than the rule. This information raises important new questions about the development and assessment of novel agents in lung cancer treatment: (1) How do we identify the most important drug targets for tumor initiation and maintenance? (2) What is the best way to assess drug candidates that may only be relevant in a small fraction of patients? (3) What models do we use to predict clinical response and identify effective combinations? And (4) how do we bring combination regimens to the clinic, particularly when the agents are not yet approved individually and may be under development from different companies? The Fifth Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was held in Cambridge, Massachusetts, on October 1-2, 2007, to discuss these questions by reviewing recent progress in the field and advancing recommendations for research and patient care. New information, conclusions, and recommendations considered significant for the field by the program faculty are summarized here and presented at greater length in the individual articles and accompanying discussions that comprise the full conference proceedings. A CME activity based on this summary is also available at www.informedicalcme.com/cme

Stereotactic Body Radiotherapy in Patients With Stage I Non–Small-Cell Lung Cancer Aged 75 Years and Older: Retrospective Results From a Multicenter Consortium

This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery

Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium

This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery