Four Head and Neck Cancer Highlights From ASCO 2013

Cabozantinib More Effective in Patients With RAS/RET Mutations

The 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), scheduled for May 31-June 4 in Chicago, features a collection of over 4,700 abstracts focused on the latest research in oncology. The meeting draws over 30,000 attendees from around the world, with the overarching theme in 2013 of Building Bridges to Conquer Cancer. This article summarizes 4 abstracts that will be discussed at the meeting that are focused on the treatment of patients with head and neck cancer.The presence of certain RET mutations impacts the effectiveness of treatment with cabozantinib in patients with medullary thyroid cancer (MTC), according to a subanalysis of the phase III EXAM trial.

Of the 215 patients enrolled in the EXAM trial who had their RET status determined, 79% harbored an activating mutation in RET while 21% were RET wild-type. Overall, all patients responded favorably to treatment with cabozantinib, an oral therapy that inhibits mutations in MET, VEGFR2, and RET. However, patients with RET mutations experienced a median progression-free survival (PFS) of 60 weeks compared with 25 weeks in those with wild-type tumors (P = .0001). Additionally, researchers noted, patients with the poor prognostic mutation RET M918T experienced a median PFS of 61 weeks compared with 36 weeks for patients with all other types of RET mutations (P = .009).

In all, 16 of 85 patients with unknown or wild-type RET mutations tested positive for RAS mutations. These patients demonstrated similar response rates and median PFS as those with RET-mutated tumors (47 weeks compared with 60 weeks, respectively).

Sym004 Effective in Heavily Pretreated Patients

The authors concluded by noting that hazard ratios indicate a PFS improvement for all RET subgroups of patients receiving treatment with cabozantinib with the extent of benefit depending on RET genotype. (Abstract 6000)The novel investigational agent Sym004 demonstrated clinical activity in heavily pretreated patients with squamous cell carcinoma of the head and neck (SCCHN), according to a proof of concept study.

Sym004 targets non-overlapping epitopes on EGFR with a first-in-class antibody mixture. In the pilot study, Sym004 was examined in 26 patients following progression, including 23 patients whose disease had progressed after receiving a prior anti-EGFR monoclonal antibody.

At the first analysis, 20 patients were evaluable by predefined criteria. In all, eight patients experienced tumor shrinkage and 14 patients had stable disease. The median progression-free survival (PFS) was 82 days (95% CI, 41 — 140) and the 24-week PFS rate was 12% (95% CI, 1–39). Additionally, treatment with Sym004 resulted in a marked downregulation of EGFR. During treatment 25 of the 26 patients (96%) developed skin rash, a common side effect of EGFR inhibition.

HPV Status Associated With Superior Clinical Outcomes

These findings indicate that Sym004 is clinically active in heavily pretreated, predominately HPV-negative patients with advanced SCCHN, which represents a hard to treat patient population with a poor prognosis. (Abstract 6002)An association between HPV status and significant improvements in clinical outcomes has been identified for patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This marks the first analysis to positively identify a correlation between HPV-positivity and favorable response rates and an overall survival benefit in this setting, the authors of the study said.

In this analysis, samples from two ECOG trials were interrogated by ISH for HPV DNA and tumor p16 status. Additionally, ERCC1 expression was assessed using the HistoRx PM-2000 tissue analysis platform. From these trials, 11 tumors tested positive for HPV, 12 were p16-positive, and 54 were HPV-negative and p16-negative.

Patients with HPV-positive tumors were found to have higher objective response rates (ORR) at 67% compared with 22% among HPV-negative tumors. Additionally, those with p16-positive tumors experienced an ORR of 60% compared with 22% in p16-negative tumors. In addition to response, overall survival greatly favored HPV-positive and p16-positive tumors, with a hazard ratio of 2.66 (P = 0.02) and 2.27 (P = 0.04), respectively.

Panitumumab Improves PFS, With Caveats

Tumors testing high for ERCC1 demonstrated favorable outcomes with variation observed based on treatment. For patients treated with cisplatin/5-FU, ORR was 58% in patients treated with the ERCC1 low regimen compared with 29% in patients treated with the high regimen. However, in patients treated with cisplatin/paclitaxel, ORR was 33% for the low regimen versus 56% for the high regimen. The overall survival hazard ratio for ERCC1 high versus low was 1.96 (P = .11). (Abstract 6006)The addition of panitumumab to cisplatin and docetaxel increased progression-free survival (PFS) and objective response rate (ORR) in patients with head and neck cancer, compared with docetaxel and cisplatin alone.

In the phase II PARTNER trial, 103 patients were randomized to receive docetaxel plus cisplatin with or without panitumumab as a first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck.

Patients who received panitumumab experienced a median PFS of 6.9 months compared with 5.5 in the cisplatin plus docetaxel alone arm (hazard ratio [HR] = .063; 95% CI, 0.40 - 1.00). Additionally, the objective response rate was 44% with panitumumab compared to 37% without. However, the median overall survival was 12.9 months with panitumumab compared with13.8 months among patients who did not receive the drug (HR = 1.10; 95% CI, 0.71 - 1.72). Moreover, the addition of panitumumab resulted in a higher incidence of grade 3/4 adverse events (73% vs 56%).

In the abstract, researchers explained that 57% of the patients treated with cisplatin and docetaxel alone were permitted to crossover to receive treatment with panitumumab after progression. This crossover event likely confounded the interpretation of survival. (Abstract 6029)

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