Advancements in molecular biomarker technology have been evolving quite significantly during the past year and have helped lead to new clinical applications of these predictive and prognostic factors. These molecular biomarkers have helped researchers find more effective clinical roles for established chemotherapies, and also for targeted therapies for treating NSCLC.  As revealed from our direct measurements and from the references in the literature and other data sources, these technological advancements are evolving and emerging so rapidly that many oncologists are not able to remain current with all of the applications of this new information, and so this represents a major practice gap for the treatment of NSCLC. Thus, a comprehensive understanding of both the science and of the practical aspects, or “how to use” the state-of-the-art molecular biomarker technology is clearly needed. One goal of the Second Annual Symposium on Personalized Therapies and Best Clinical Practices for Lung Cancer and Head & Neck Cancer is to close this practice gap resulting from the rapid advancement of biomarker technology.

The clinical applications of predictive and prognostic molecular biomarkers, including histology, gene mutations and other factors are becoming critically important for the selection of and usage of chemotherapies for NSCLC. Thus, there is a practice gap and a need to educate oncologists on how to actually apply these predictive and prognostic tests for developing personalized treatment strategies for patients with NSCLC.

The clinical applications of chemotherapy for NSCLC have heretofore been based on established and empirically derived first-line, second-line and third-line therapies.  However, now there is data to show that the expression of specific cellular proteins such as ERCC-1, RRM1, Beta tubulin, SPARC and others may predict patient response to specific chemotherapy agents including taxanes, platinums and antimetabolites, and, also predict patient prognosis. There is also recent data that shows that tumor histology can be predictive of response to specific chemotherapy agents. It is quite clear that NSCLC patients with adenocarcinoma or large cell histological sub types respond better to certain drugs, such as pemetrexed. These histology-based response differences were further corroborated by data presented at the 2009 ASCO meeting with results from a randomized Phase III trial of best supportive care (BSC) versus pemetrexed. Moreover, this clinical trial revealed an important new role for this chemotherapeutic agent, that of maintenance therapy for NSCLC until disease progression. Pemetrexed maintenance therapy offered Progression-Free Survival (PFS) and Overall Survival (OS) that was significantly superior to BSC. There is a gap that exists with many oncologists’ understanding of how to optimally incorporate this chemotherapy agent into maintenance therapy of NSCLC.

The clinical applications of targeted therapies for many patients with NSCLC are critically important for improved survival and quality of life. Although the use of anti-angiogenesis therapy is now standard in patients with non-squamous histology, there remains some questions-in-practice regarding its use. These have included, “what is the optimum dose and duration of anti-angiogenesis therapy?” and “should anti-angiogenesis therapy be continued as maintenance therapy after the patient has progressed from first-line therapy?” How an anti-angiogenesis approach can be optimized in a multi-modality approach to NSCLC treatment is yet another question-in-practice. Final results from the AVAil trial were presented at the 2009 ASCO meeting that further demonstrated the efficacy of bevacizumab in combination with platinum-based chemotherapy in the treatment of advanced NSCLC. And final safety data on AVAil confirmed the well-established and manageable safety profile of bevacizumab-based therapy in patients with advanced NSCLC. Results from a randomized, double blind, placebo controlled, Phase IIIb, clinical trial (ATLAS) were presented at the 2009 ASCO meeting. These data showed that the addition of the anti-antiogenic agent, bevacizumab, plus the anti-EGFR agent, erlotinib, significantly prolonged the PFS of patients with NSCLC in the maintenance setting following first-line combination systemic therapy. Thus, a physician practice gap exists regarding the use of anti-angiogenesis therapy in the treatment of NSCLC.

Therapies that target the EGFR pathway are also increasingly important for many patients with NSCLC. There have been several scientific advancements that may change how anti-EGFR therapy can be optimally applied in a personalized approach to NSCLC treatment. Factors such as EGFR expression and mutation status have been shown to be important for response to anti-EGFR therapy. Positive results from two clinical trials presented at the 2009 ASCO meeting were revealed that showed the efficacy of gefitinib as a single-agent therapy in patients with an EGFR mutation. One was a randomized, open-label, Phase III trial in selected patients with advanced NSCLC (IPASS) revealing the significant efficacy of single-agent gefitinib therapy in patients with an EGFR mutation, and showing that EGFR mutation status was a strong predictor of response to this agent. The other was of a similar design, but as of May 2009 there has only been the announcement at the 2009 ASCO meeting of a planned preliminary analysis for PFS. No results were released at the 2009 ASCO meeting. Also presented at the 2009 ASCO meeting regarding anti-EGFR therapy for patients with advanced NSCLC were the results from the SATURN trial, a double-blind, randomized, Phase III study of maintenance erlotinib. The SATURN trial met both its primary and co-primary endpoints with high statistical significance. Erlotinib in the maintenance setting significantly improves disease control and delays disease progression.

Some clinical studies have also shown that the mutation status of the Kras oncogene may also be another predictive factor for response to anti-EGFR therapy. However, results from one trial presented at the 2009 ASCO meeting showed that the updated clinical data from the FLEX trial (presented in 2008) did not support the previously raised hypothesis that the Kras mutation is predictive of cetuximab efficacy when combined with first-line chemotherapy of advanced NSCLC, whereas an early acne-like rash of any grade appears to be associated with a better outcome in patients treated with platinum-based chemotherapy plus cetuximab in this setting. And a retrospective analysis from another clinical trial using an anti-EGFR approach for NSCLC presented at ASCO 2009 (BMS099) showed that there was no significant correlation between patient response to cetuximab and any molecular marker evaluated to date (including Kras mutation, EGFR mutation, EGFR by IHC, and EGFR by FISH). Moreover, an analysis of the SATURN trial data showed that the efficacy of erlotinib was similar in both the wild type and mutant Kras  patients. Thus, the optimal roles of anti-EGFR therapy and the optimal selection of anti-EGFR patients and regimens for treating advanced NSCLC are areas that are evolving. Therefore, another goal of the Second Annual Symposium on Personalized Therapies and Best Clinical Practices for Lung Cancer and Head & Neck Cancer is to close these physician practice gaps regarding anti-EGFR treatment strategies.

Regarding recent developments in second-line therapy for patients with advanced NSCLC, results from a Phase III trial (ZODIAC) were presented at the 2009 ASCO meeting. The ZODIAC trial was the first study to show a significant clinical benefit of adding a targeted therapy to a chemotherapy agent for advanced NSCLC. In this trial, vandetanib, a small molecule inhibitor of VEGFR, EGFR and RET, in combination with docetaxel, met its primary endpoint of prolonging PFS versus docetaxel alone.

According to various sources, including www.clinical trials.gov, pharmaceutical company press releases, and, pharmaceutical company Web sites, as of June 2009 there are ten investigational drugs for lung cancer in Phase III trials and five in Phase II trials. These investigational agents include targeted therapies and chemotherapies. They include IGF-1R agents, various tyrosine kinase inhbitors including multiple and dual pathway inhibitors, vaccines, anti-EGFR and anti-VEGF monoclonal antibodies, a platinum agent, and an anthracycline.

Head & Neck Cancer

The treatment of Head and Neck Cancer (HNC) in patients with locally-advanced, recurrent, or metastatic disease remains quite challenging. Long-term survival varies from 10% to 50%, depending upon the site, stage and resectability of the tumor. Surgical intervention is potentially curative in resectable patients. However, preservation of organ structure and function is a major concern. Chemotherapy before definitive surgery and radiation therapy has been demonstrated to increase response in both localized disease and disease with lymph node metastasis. At the 2009 ASCO annual meeting, data from a Phase III clinical trial (Hitt) stated that for unresectable, locally-advanced HNC, induction chemotherapy with docetaxel, cisplatin and 5-FU should now be considered a standard of care.  How chemotherapy can be optimally applied in a personalized approach to the treatment of HNC is a current question-in-practice and practice gap.

Improved results have been observed with the clinical applications of targeted therapies for HNC. The optimal roles of targeted therapies such as anti-EGFR strategies in the treatment of HNC are areas that are rapidly evolving and, thus, represent an identifiable physician practice gap. At the ASCO 2009 meeting, proteomics helped provide further support for using anti-EGFR monotherapy with either erlotinib, gefitinib or cetuximab for squamous cell HNC. Thus, there is a practice gap and an educational need to review and evaluate the most up-to-date data regarding the clinical application of anti-EGFR other targeted therapies for the treatment of patients with HNC. Preliminary results from one Phase II trial reported at the 2009 ASCO meeting suggested that sorafenib may be a useful agent in treating patients with thyroid cancer.

The OLC has conducted a very extensive physician practice gap analysis and needs assessment.  As a result, we have determined that these activities are urgently needed. The primary objective of the Second Annual Symposium on Personalized Therapies and Best Clinical Practices for Lung Cancer and Head and Neck Cancer and its enduring materials is to provide oncologists with the knowledge and competence enabling them to develop subsequent practice performance changes so that they can treat their patients with thoracic malignancies with the optimal personalized approaches in order to improve patient outcomes and minimize drug-induced toxicities.  These CME activities are especially designed to help oncologists close several very important gaps in their practices arising primarily from the significant practice-changing data on thoracic malignancies presented at the recent 2009 annual ASCO meeting.

Before the symposium begins, a pre-activity educational assessment consisting of approximately six to ten patient care treatment-strategy questions with multiple-choice answers will be conducted with the learners to determine how they currently treat their patients with lung cancer or head and neck cancer in order to determine a baseline of current medical oncologists’ practices. This will be accomplished at the live course using the Audience Response System (ARS).

The format of the symposium is that all of its sessions will contain at least one major interactive patient case study with multiple-choice treatment ARS questions for the learners, and one Point-CounterPoint debate whereby the learners interact with the faculty via ARS.  The faculty has been instructed to begin each didactic presentation with a patient case study or a few clinical questions and ARS for providing additional learner involvement with the faculty at this symposium.  This approach utilizing case studies or clinical questions to start each didactic presentation was initially used by the OLC at the Second Annual Symposium on Personalized Therapies and Best Clinical Practices for Breast Cancer that we conducted in January 2009 as a beta test, and it was highly successful.

Each session of the symposium will conclude with a 15-minute “consensus” period with a Q & A and panel discussion during which the following three questions are asked of the session’s faculty regarding the particular session’s content to help ensure that the content can be applied to clinical practice today:  1) Is this a new standard of care?   2) Should it be discussed with your patients?   3) How can you use it today in your practice? The learners will express their opinions via ARS after the Q & A and faculty “consensus” discussion and will either agree or disagree with the faculty.  Further opportunities for learners’ questions are provided during these consensus periods.  And, including these novel consensus periods in our symposia has, indeed, helped ensure that knowledge and competence that is useful today is presented, rather than data that is not ready for the clinic.

The following is an overview of each session.
Session 1: Personalizing Chemotherapy and Best Clinical Practices will be chaired by George Simon, MD, Director of the Thoracic Oncology Program of the Fox Chase Cancer Center in Philadelphia, PA.  This session is a review of the key new clinical and scientific data that will help oncologists treat their lung cancer and head and neck cancer patients with personalized chemotherapies and with best clinical practices. The first presentation in this session begins with a key question in practice, “have personalized regimens of chemotherapies and targeted therapies achieved what they should have?  This question starts with a review of the data, “where systemic therapy has been until now” for the treatment of thoracic malignancies.  It then addresses how to personalize chemotherapy for treating thoracic malignancies utilizing the newest molecular biomarkers and tests.  It also reviews the data regarding the new concept of using maintenance chemotherapy for Non-Small Cell Lung Cancer (NSCLC).  And it reviews the newest data regarding combined-modality treatment for treating Head and Neck Cancer (HNC) with a personalized approach and with best clinical practices. The final didactic presentation in this session is on new data regarding the treatment of Small Cell Lung Cancer with best clinical practices. Session 1 continues with an interactive Point-CounterPoint debate on the subject of “have we reached the maximum benefit from chemotherapy for NSCLC?”  Following the debate is an interactive patient case study to review the best clinical practices using chemotherapy for thoracic malignancies considering the new data from ASCO 2009.  The learners participate via ARS by selecting from various treatment options. Session 1 concludes with a Panel Discussion and a Q & A Consensus Period to help ensure that the data presented can be applied in the clinic today. And the learners are further involved through the use of ARS voting and direct questioning of the faculty.

Session 2:  Personalizing Anti-Angiogenesis Therapy and Best Clinical Practices will be chaired by Joan Schiller, MD, Deputy Director of the Harold C. Simmons Cancer Center, UT Southwestern Medical Center in Dallas, TX.  Session 2 is a review of the new key clinical and scientific data that will help oncologists treat their NSCLC and HNC patients with optimal and personalized anti-angiogenesis therapies.  Here, too, much of the data presented is from clinical trials presented at the recent 2009 ASCO meeting regarding the personalized use of anti-angiogenesis therapies for thoracic malignancies.  The session also includes a presentation on the new data with anti-angiogenic therapy regarding the new concept of maintenance therapy of NSCLC, and, data on the use of a dual-targeted therapy approach with an anti-angiogenesis agent plus an anti-EGFR agent for NSCLC.  Session 2 includes a didactic presentation posed as another question in practice, “can we personalize the use of radiation therapy with targeted therapies?” And like the other sessions, this session includes a Point-CounterPoint debate, which here is on the issue of whether or not the combination of chemotherapy plus an anti-angiogenic agent is the standard of care for NSCLC.  Following the debate is an interactive patient case study to review the best clinical practices using anti-angiogenic therapy for thoracic malignancies, considering the new data from ASCO 2009.  And, again, like all sessions, Session 2 concludes with a Panel Discussion and Q & A Consensus Period to help ensure that the data presented can be applied in the clinic today. ARS and direct questioning of the faculty are again used for the debate and the Consensus Period to engage the learners.

“Lunch with the Professors” follows the first half of Session 2 to provide the learners with an additional opportunity to interact with the faculty.  Each faculty member is assigned one table for lunch, and learners are invited on a first-come basis to sit and converse with the faculty of their choice.  This also provides an additional hour of CME credit.

Session 3:  Personalizing Anti-EGFR Therapy and Best Clinical Practices will be chaired by Thomas Lynch, MD, Director, Yale Cancer Center, and Physician-in-Chief, Smilow Cancer Hospital, Yale-New Haven, New Haven, CT.
This session is a review of the new key clinical and scientific data that will help oncologists treat their NSCLC and HNC patients with optimal and personalized anti-EGFR therapies. This session’s format is similar to that of the first two sessions, with new data presented and reviewed on personalizing therapies for thoracic malignancies, but here the focus is with anti-EGFR strategies.  The Point-CounterPoint debate topic in this session is that all patients should be screened for the EGFR mutation.  This session concludes with two case studies (one on the best clinical practices and the other on a unique case regarding a patient who progresses after a year of maintenance therapy with a small molecule anti-EGFR agent), a Panel Discussion, Q&A and a Consensus Period. ARS is again used for the debate and the Consensus Period to engage the learners. One unique and new presentation in this session addresses the subject of yet another key question in practice, “how do we better involve our pathologists to do more EGFR and Kras testing?” This presentation will be a review of the different EGFR assays and how to best use them, and it will be presented by one of the leading thoracic cancer pathologists in the USA, Mark Ladanyi, Chief, Molecular Diagnostics Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center in New York, NY.

Session 4:  Investigational Agents for Lung Cancer will be chaired, and its one and only presentation will be given by Roy S. Herbst, MD, PhD, Chief, Section of Thoracic Oncology, Professor of Medicine & Cancer Biology, Department of Thoracic/Head & Neck Medical Oncology, and Co-Director, Phase I Clinical Trials Working Group The University of Texas, M.D. Anderson Cancer Center in Houston, TX. This session is a review of the fifteen investigational agents in late-stage development for both NSCLC and SCLC. Ten drugs are in Phase III trials and five are in Phase II trials.  This will be a twenty-minute didactic presentation followed by a ten-minute Q & A between the audience and faculty.  The objective of this session is to ensure that the community-based, non-academic oncologists treating lung cancer are aware of the many therapeutic options for their patients besides the drugs that are currently available on the market.

The symposium concludes with the re-asking of the six to ten pre-test questions via ARS, but at this time the questions are rephrased into the future tense to help determine if the learners are likely to change their practices based upon the knowledge and competence they have acquired during the symposium. The pre-and post-test question answers will be compared and discussed by the faculty and the learners will be afforded one final opportunity for questioning the faculty.

The format of this symposium versus last year’s symposium has been shortened by four hours at the request of the participants of our recent annual symposia on personalized therapies.  These participants and other oncologists that we have surveyed with live interviews and focus groups clearly stated to us that with a one-day symposium they would more likely attend because they would bring their spouse/significant other and spend one of the two weekend days out of town, site seeing together.  And Philadelphia was chosen because of feedback from the past participants. It is worth noting that more than 75% of the audience of learners at all of our previous personalized therapy symposia traveled from states in the USA other than the state of the live symposium.  In fact, at the January 2009 personalized breast cancer symposium, learners from 31 different states other than Florida, participated.

The content eliminated from last year’s symposium was data regarding specific surgical techniques, and data regarding the use anti-emetic and bone metastases.  Otherwise, the main content of the symposium has actually been expanded to include more data on the use of systemic drug therapy alone, and, in combined modality treatment settings. This change of additional content devoted to systemic therapy was actually necessary in order to help oncologists close their practice gaps, considering the volume of new clinical data on NSCLC and HNC.

As required by the ACCME, the content of this symposium and corresponding enduring materials has been designed to address the relevant physician competencies and desirable attributes through the use of both the Institute of Medical Competencies (IOM) and the American Board of Medical Specialties (ABMS) criteria.  This is discussed in detail later in this document.

These educational activities are designed to meet the educational needs of medical oncologists, hematologist/oncologists, radiation oncologists, surgical oncologists, pathologists, nurse practitioners/nurses, pharmacists, fellows and other health care professionals who are involved in the treatment or management of patients with lung cancer or head and neck cancer.  These thoracic malignancies are treated optimally by a multi-disciplinary approach of clinicians and, thus, they are all targeted for invitation to these educational activities.

Based on the data identified in the Needs Assessment and Physician Practice Gap Analysis, the following Educational Objectives have been developed for these CME activities:

1. Evaluate the roles of predictive and prognostic molecular biomarkers for the treatment of thoracic malignancies.
2. Devise strategies to apply predictive and prognostic tests in the clinic in order to help develop personalized systemic therapy regimens for optimal treatment of patients with thoracic malignancies.
3. Evaluate the roles of histology in the development of optimal treatment strategies for systemic therapy of thoracic malignancies.
4. Evaluate the roles of gene mutations in the development of optimal treatment strategies for systemic therapy of thoracic malignancies.
5. Analyze the large amount of new clinical data revealed in 2009 for personalization of treatments for patients with thoracic malignancies receiving first-line therapy and for those who are refractory to prior treatment, and, for NSCLC patients receiving maintenance therapy.
6. Determine the optimal roles of chemotherapies, including anti-metabolites, multi-targeted antifolates, taxanes and platinums for the personalized treatment of patients with thoracic malignancies.
7. Determine the newest applications of targeted therapies, including combinations of anti-angiogenesis agents and combinations of anti-EGFR agents in the first-line and maintenance settings, single-agent anti-EGFR therapy in the first-line setting, and other targeted approaches for the treatment of patients with thoracic malignancies.
8. For maintenance or consolidation therapy of NSCLC, devise the best clinical practice treatment strategies using chemotherapy, including multi-targeted antifolates, and also using targeted therapy, including anti-EGFR and anti-angiogenesis approaches, to increase PFS.
9. Devise strategies to optimize multi-modality approaches for the personalized treatment of HNC with best clinical practices: the use of HPV and p16 molecular biomarkers for improved prognosis, and the use of blood-based testing to select HNC populations to receive anti-EGFR monotherapy.
10. Evaluate clinical data revealing a new standard of care using induction chemotherapy with a taxane and a platinum followed by consolidation RT for locally advanced HNC.
11. Compare and contrast the clinical efficacy of the numerous investigational new drugs in late-stage development for treating lung cancer.

The Oncology Learning Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Oncology Learning Center designates this educational activity for a maximum of 9 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

During the live course, learners will have ample time to interact with the faculty via the numerous Q & A sessions and with microphones to communicate directly with the faculty.  Through numerous case studies the learners will use their ARS handsets to select treatment strategies, and the learners will also answer other clinical and scientific questions that the faculty will ask during their didactic presentations.  Point-CounterPoint debates and Consensus Periods are yet additional opportunities for learner involvement with the faculty, again, using ARS.