Correspondence

Cetuximab in Head and Neck Cancer

N Engl J Med 2008; 359:2725-2726December 18, 2008

Article

To the Editor:

The study of chemotherapy plus cetuximab in patients with head and neck cancer, reported by Vermorken et al. (Sept. 11 issue),1 is limited by the fact that enrollment was restricted to patients with a good Karnofsky performance score (70 or more). The subgroup analysis indicated that patients with a Karnofsky performance score between 70 and 80 did not benefit from treatment with cetuximab. Many patients with recurrent squamous-cell carcinoma of the head and neck present with a much worse performance status than those enrolled in the study by Vermorken et al.2 Therefore, whether the addition of cetuximab to platinum–fluorouracil chemotherapy can benefit such patients is unknown. The baseline quality of life is an important predictor of responsiveness to chemotherapy in advanced head and neck cancer.3 Although Vermorken et al. measured quality of life, they do not present details concerning the instruments they used to estimate it. It is unclear why baseline quality-of-life data were available for only 227 of 442 patients in this prospective trial.

Orlando Guntinas-Lichius, M.D.
Friedrich-Schiller University Jena, D-07740 Jena, Germany
orlando.guntinas@med.uni-jena.de

3 References

1
Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-1127
Full Text | Web of Science | Medline

2
Argiris A, Li Y, Forastiere A. Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. Cancer 2004;101:2222-2229
CrossRef | Web of Science | Medline

3
Karvonen-Gutierrez CA, Ronis DL, Fowler KE, Terrell JE, Gruber SB, Duffy SA. Quality of life scores predict survival among patients with head and neck cancer. J Clin Oncol 2008;26:2754-2760
CrossRef | Web of Science | Medline

To the Editor:

The study by Vermorken and colleagues shows the superior response of head and neck cancer to cetuximab plus platinum-based chemotherapy as compared with chemotherapy alone. Nevertheless, it is still unclear whether cetuximab should always be combined with first-line chemotherapy.

For incurable cancers, response or progression-free survival is not always the goal of treatment. Survival with sequential treatment is often similar to survival with upfront, concurrent treatment, but with less toxicity.1-4 It also spares patients the burden of treatment, as compared with concurrent therapy followed by maintenance.

Cetuximab, either alone or with chemotherapy, is now widely used for head and neck cancer. In the study by Vermorken et al., only 6% of patients in the control group received cetuximab, and then only after the end of the study. Had cetuximab been given to these patients at the time of disease progression, the difference in survival between the two groups could have been smaller. Moreover, more patients in the cetuximab group were treated with cisplatin. This imbalance between the groups could explain the superior results in the cetuximab group, because responses to cisplatin are more frequent than responses to carboplatin.1,5

Tawee Tanvetyanon, M.D.
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612
tanvett@moffitt.org

5 References

1
Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 1992;10:1245-1251
Web of Science | Medline

2
Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer: a randomised controlled trial. Lancet 2007;370:143-152[Erratum, Lancet 2007;370:566.]
CrossRef | Web of Science | Medline

3
Sledge GW, Neuberg D, Bernardo P, et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 2003;21:588-592
CrossRef | Web of Science | Medline

4
Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 2004;292:470-484
CrossRef | Web of Science | Medline

5
Ardizzoni A, Boni L, Tiseo M, et al. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 2007;99:847-857
CrossRef | Web of Science | Medline

Author/Editor Response

Guntinas-Lichius suggests that many patients with recurrent head and neck cancer will not be suitable candidates for treatment with platinum–fluorouracil plus cetuximab. We disagree. Our study shows that patients with a Karnofsky performance score of 70 or more who can tolerate platinum–fluorouracil can also tolerate platinum–fluorouracil plus cetuximab. These patients, and those with lower Karnofsky scores, are typical of patients who enroll in randomized trials that use the standard platinum–fluorouracil regimen.1-3 The subgroup analyses do not allow us to state with certainty that some groups do not benefit from cetuximab, or to suggest the degree of benefit from cetuximab in such groups. Actually, the effect of cetuximab on the response rate was higher among patients with a Karnofsky score of less than 80 (26% with cetuximab plus platinum–fluorouracil vs. 4% with platinum–fluorouracil alone) than among those with a higher score (37% vs. 22%).

Guntinas-Lichius also mentions that baseline quality of life is a significant predictor of the outcome. In our study, the baseline quality-of-life score was based on items 29 and 30 of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ-C30), which reflect overall health and quality of life during the week before the quality-of-life test (the results of the quality-of-life analysis have not yet been published). The reason that the global quality-of-life score at baseline was available for only about half the patients was that completion of the quality-of-life questionnaire was not required for eligibility.

In response to Tanvetyanon's question: the study was not designed to address whether concurrent cetuximab–chemotherapy is superior to sequential treatment. However, the separation of survival curves at an early time point suggests a synergism between cetuximab and chemotherapy. A clinical benefit was obtained in about 80% of patients, and phase II studies suggest a clinical benefit of about 50% with cetuximab monotherapy in patients who have not had a response to platinum,4 which suggests that concurrent treatment is beneficial. The fact that cisplatin was given to slightly more patients in the cetuximab group is an unlikely explanation of our results.

Jan B. Vermorken, M.D., Ph.D.
Antwerp University Hospital, 2650 Edegem, Belgium
jan.b.vermorken@uza.be

for the EXTREME Investigators

4 References

1
Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 1992;10:1245-1251
Web of Science | Medline

2
Jacobs C, Lyman G, Velez-Garcia E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 1992;10:257-263
Web of Science | Medline

3
Clavel M, Vermorken JB, Cognetti F, et al. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 1994;5:521-526
Web of Science | Medline

4
Vermorken JB, Herbst RS, Leon X, Amellal N, Baselga J. Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies. Cancer 2008;112:2710-2719
CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1
Jens Büntzel, Oliver Micke. (2009) Second-line chemotherapy in head and neck cancer: what should we expect?. Expert Review of Anticancer Therapy 9:3, 269-273
CrossRef