Monday HN Sessions

Post by Matthew G. Fury, MD, PhD:

At the Clinical Science Symposium, Abstract 6002 summarized the final results of a phase II study of sorafenib for patients with advanced thyroid cancer (n = 55 patients). Efficacy was encouraging, with an objective response rate of 36% and median overall survival of 140 weeks. A randomized phase III study is planned.

Abstract 6046 summarized the results of a phase II study for locally advanced nasopharynx cancer, in which patients received induction TPF (two to four cycles) followed by definitive RT + cisplatin. Among 45 patients, 60% had stage IV disease. IMRT was given for 76% of patients. Objective response rate after TPF was 87%, and 2 year OS was 85%. Although most NPC trials have administered adjuvant PF after chemoradiation, perhaps the order should be reversed. This question merits further study.

Abstract 6042 was a retrospective comparison of RT + cisplatin versus RT + cetuximab as definitive treatment of locally or regionally advanced HNSCC at a single institution. Among 175 patients, approximately 2/3 of patients were treated with cisplatin + RT. Compared to the patients treated with cetuximab + RT, patients treated with cisplatin + RT had better KPS and better outcomes for all efficacy endpoints. In contrast, at the oral session on Saturday, Abstract 6010 showed no difference in the primary endpoint of the study (larynx preservation) among 153 patients with stage III/IV SCC of larynx/hypopharynx randomized to RT + cisplatin versus RT + cetuximab. However, all patients in Abstract 6010 received induction TPF prior to randomization. With recognition of the potential for cumulative toxicity with platinum, the use of induction TPF prior to randomization may have had a detrimental effect on platinum tolerability in Abstract 6010. As such, we still do not have the definitive answer to the question of the relative efficacy of these two drugs in the combined modality setting.

HN Saturday Oral Session

Post by Matthew G. Fury, MD, PhD:

In Abstract 6009, Hitt presented final results of a randomized phase III study comparing induction chemotherapy (TPF or PF) followed by chemoradiotherapy (CRT) versus CRT alone for patients (n = 439) with unresectable HNSCC. The primary endpoint was time to failure. The authors presented this as a positive study, but as pointed out in the discussion, many patients were not included in the final analysis (33 patients in the PF arm, 44 patients in the TPF arm). We await analysis of this study according to intention-to-treat principles.

Gillison (Abstract 6003) and Rischin (Abstract 6004) reported retrospective analyses of HPV status among patients treated prospectively on randomized clinical trials (RTOG 0129 and HEADstart, respectively), re-demonstrating that positivity for HPV appears to be an independent predictor of improved survival. The Gillison abstract demonstrated that the hazard of death was lowest for HPV-positive patients who did not have a significant history of tobacco use (less than 20 pack years).

Abstract 6007 presented final results of the DAHANCA 10 trial, a randomized study of the effects of darbepoetin alpha among patients receiving accelerated fractionated RT. Eligible patients had baseline hemoglobin less than 14.0 g/dL, and were randomized to weekly darbepoetin plus RT or RT alone. In the darbepoetin group, outcomes were inferior for locoregional control, disease free survival, and overall survival (p = 0.07). This result is consistent with the reports of others, and points to the importance of following established ASCO/ASH guidelines for the use of erythropoiesis-stimulating agents.

HN Friday Poster Discussion

Post by Matthew G. Fury, MD, PhD

As one would expect in a poster session, no practice-changing studies were reported. However, there were intriguing observations in several topic areas.

Biomarkers: Seiwert (abstract 6033) reported a tissue microarray analysis of tumors from 60 HNSCC patients treated with the THFX regimen, in which a panel of 5 DNA repair markers appeared to predict overall survival. It will be exciting to see if these results hold up in larger studies of HN patients treated with platinum-based chemoradiotherapy.

Immunotherapy: Wirth (abstract 6025) described an autologous cytotoxic T cell (CTL) product that is directed against EBV-positive NPC. In this small study, one patient treated with EBV-CTLs experienced complete response and one patient had prolonged stable disease. The discussant pointed out that this CTL strategy would be an attractive topic for study in the adjuvant setting.

Anti-angiogenesis: Meluch (6012) and Pfister (6013) studied the addition of bevacizumab to combined modality regimens for locally advanced disease. (The Meluch study regimen also included erlotinib). Toxicities were generally consistent with those that would be expected in the combined modality setting, but 2 treatment-related deaths in the Meluch study (perforated diverticulum, CVA) were possibly due to bevacizumab. Efficacy results in both studies compared well to historical controls, but larger randomized studies would be needed to determine if bevacizumab has role in the combined modality setting. The changing face of HN cancer was evident in the Pfister study, in which HPV-positivity was identified in most of the tumors that were tested.

Induction Chemotherapy: Tahara (6021) reported on the phase I development of a novel induction chemotherapy regimen called “TPS,” in which the oral fluoropyrimidine S-1 replaces 5-FU. Replacement of 5-FU infusion with oral S-1 has clear logistical appeal, and it would be interesting to see this TPS regimen compared with TPF in prospective randomized studies.