For this month and next month, Dr Christy Russell and I will be covering some of the data from this year’s American Society of Clinical Oncology^® (ASCO) meeting. In this edition, I will review for you a number of the presentations and posters concerning hematologic malignancies, gastrointestinal (GI) cancers, lung cancer and head & neck cancers. In August, Dr Russell will cover breast cancer, genitourinary (GU) cancers, and other areas.

Presentations from the Head and Neck Cancer Sessions at The Annual Oncology Meeting

There were 3 presentations in this section that I believe are worth reviewing:

In recent years, there have been a number of clinical trials examining the potential value of several novel targeted agents in well-differentiated thyroid cancer. We have seen trials with AMG706, vandetanib, pazopanib, sunitinib, axitinib and others. Also, in the last several years, it has been discovered that the BRAF gene is mutated in 60% to 70% of well-differentiated (WD) thyroid cancers and that this mutation, BRAF^V600E, is associated with larger tumors, higher number of involved lymph nodes and with nodal extra-capsular extension. These are very vascular tumors with high VEGF levels and genetic changes that involve the MAP kinase and PI3K/Akt pathways.

Generally, higher risk patients within the WD thyroid cancer population include males, those >45 years of age, tumors >4 cm in diameter, tumors with extra-thyroidal extension and those with metastatic lesions. Although the long term prognosis is very good for stage I and II patients, patients with nodal involvement and/or metastatic disease do not do nearly as well, frequently requiring multiple therapeutic interventions over the course of their disease. Standard chemotherapeutic agents have minimal activity in these advanced disease patients.

Abstract 6002: Effect of BRAF^V600E on response to sorafenib in advanced thyroid cancer patients by Dr Marcia Brose, et al

Fifty-five patients were administered sorafenib 400 mg BID. Responses were monitored by computed tomography (CT) and positron emission tomography (PET) scanning. Twenty-five patients had papillary carcinoma, and 25 patients had follicular/Hurthle cell carcinoma. Some patients responded very quickly within 8 weeks, but others responded much more slowly. Thirty-six percent of patients achieved PR, and 46% achieved stable disease (SD) for a clinical benefit rate of 82%. Responses were seen in papillary, follicular, and even in anaplastic thyroid cancer. Many of those patients with SD response had some degree of tumor regression. Progression-free survival for the total population is 63 weeks with a PFS of 84 weeks for the well-differentiated cancers. Overall survival is 140 weeks. This compares favorably with historical data reporting OS for doxorubicin therapy of 40 weeks. There is a trend toward increased PFS in patients with the BRAF^V600E mutation but it is not statistically significant at this time. The authors are now examining the impact of the BRAF gene copy number on outcome endpoints. Dr Brose and her colleagues are planning a phase III trial with sorafenib as well as a new phase II trial with sorafenib and everolimus.

Abstract 6003: Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129 by Dr Maura Gillison, et al

One of the more interesting developments in squamous cell carcinoma of head and neck (SCCHN) in recent years has been the recognition that many oropharyngeal squamous cell carcinomas are positive for the human papillomavirus (HPV) and that patients with HPV-positive oropharyngeal carcinoma have a better prognosis and may be more responsive to therapeutic intervention. Dr Maura Gillison, for the RTOG, presented the abstract. This was a phase III randomized trial comparing standard fractionation radiotherapy (XRT) + cisplatin with accelerated fractionation XRT + cisplatin. The authors compared the OS and PFS results between the HPV-positive and HPV-negative populations in this trial. Sixty-four percent of the patients were HPV-positive, and 96% of those were positive for HPV-16. Ninety-six percent of the HPV-positive tumors were also positive for p16. Nineteen percent of the HPV-negative tumors were also p16-positive. Patients who were HPV-positive were younger and more likely Caucasian. They had better performance status, were more likely to have T2-3 tumors, and they generally had less tobacco exposure than the HPV-negative group. Patients who were HPV-positive had better OS. At 5 years, the absolute difference in OS between the 2 groups was 29%: 48% for HPV-negative versus 77% for HPV-positive. Two-year outcome analysis demonstrated that OS, PFS and local-regional failure rates were all statistically in favor of the HPV-positive group. In addition, second primary tumors and second aerodigestive tumors were also less common in the HPV-positive patients. The authors next examined the impact of smoking on outcome (PFS and OS) in the HPV-positive and HPV-negative patients. Considering the HR for HPV-positive patients with <20 pack years as 1.0, the HR for HPV-positive patients with >20 pack years was 1.91. The HR for HPV-negative patients with <20 or >20 pack-years were 2.25 and 4.30, respectively. Patients who were HPV-positive who were never smokers had a 5-year PFS of 95% versus 30% for the HPV-negative heavy smokers. The status of p16 by IHC was strongly correlated with tumor HPV status and is a valid surrogate. Tobacco exposure appears to modify the biological behavior of an HPV-positive tumor. Future trials in oropharyngeal cancers must include stratification for HPV status.

Two years ago, one of the most exciting presentations at the ASCO meeting was the EXTREME trial presented by Dr Jan Vermorken where the longest survival ever seen in advanced head and neck cancer was associated with the addition of cetuximab to platinum based chemotherapy. Since then, there has been a great deal of data in colorectal cancer (CRC) demonstrating that patients who were KRAS-mutated did not benefit from cetuximab.

Abstract 6005: Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: Platinum-based CT plus cetuximab in first-line R/M SCCHN by Dr Lisa Licitra, et al

The EXTREME study demonstrated statistically significant improvements in OS, PFS and ORR with the addition of cetuximab to chemotherapy. Epidermal growth factor receptor protein expression by IHC has not been correlated with outcome in cetuximab treated patients with CRC, NSCLC or SCCHN. Epidermal growth factor receptor domain mutations also have not been correlated with cetuximab efficacy in CRC or NSCLC. What impact EGFR gene copy number has on cetuximab benefit in CRC, NSCLC and SCCHN is uncertain. This current analysis was designed to investigate the impact of EGFR gene copy number by FISH on the relative efficacy of platinum-based chemotherapy with or without cetuximab. Seventy-one percent of the study tumor specimens were available and evaluable by FISH. Approximately 30% of the patients in both treatment arms were FISH-positive by the Colorado System of analysis. When ORR, PFS and OS were examined according to EGFR gene copy number status by FISH, there were no differences in the outcome measures whether the patient tumors in the chemotherapy plus cetuximab group were FISH-positive or FISH-negative. The same was true in the chemotherapy alone arm.

The authors concluded that there was no correlation between EGFR gene copy number and benefit from chemotherapy plus cetuximab in the EXTREME study and that platinum-based chemotherapy plus cetuximab is the standard of care for first-line treatment of recurrent or metastatic SCCHN.

OncoFacts™ Editor:

James Epstein, MD

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