To the Editor—I read with great interest, in the recent issue of the Hong Kong Medical Journal, the article “Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor-activating mutation-positive non–small-cell lung cancer patients in Hong Kong” by Lee et al.1 The authors, by indirect treatment comparison, demonstrated the cost-effectiveness of erlotinib over gefitinib. However, I find it difficult to understand the rationale behind the basis of this comparison. The approach compares trial [A vs C] with trial [B vs C], using C as the bridge comparator. By substitution, the authors cited IPASS2 with gefitinib-treated patients (A) versus carboplatin-paclitaxel–treated patients (C) for comparison with OPTIMAL3 with erlotinib-treated patients (B) versus carboplatin-gemcitabine–treated patients (C). Obviously the C’s in the two trials are not identical unless it can be proven that carboplatin-paclitaxel and carboplatin-gemcitabine have exactly the same efficacy. Furthermore the patient characteristics in the two trials are also not identical. In IPASS only some patients were shown to have epidermal growth factor receptor (EGFR) mutations, while in OPTIMAL all patients had EGFR-activating mutations in exons 19 and 21. Since such mutations determine the response to treatment targeting tyrosine kinase inhibitors, patients receiving erlotinib (in OPTIMAL) had a clear advantage.

As Lam and Mok4 pointed out in their editorial commentary, head-to-head comparison is the preferred method of assessment and such studies have been done in Korea, Taiwan and China, showing no significant difference in efficacy between gefitinib and erlotinib except a better toxicity profile for the former. I fully agree with the editors that we should move on beyond these two drugs.

As to cost-effectiveness, it might be worthwhile to take note of a third EGFR inhibitor, icotinib. In a head-to-head comparison trial,5 it has been shown to be non-inferior to gefitinib but with an even better toxicity profile. Developed in China, it is said to cost considerably less than either erlotinib or gefitinib. Hope it becomes available in Hong Kong soon.

No conflicts of interests were declared by author.

1. Lee VW, Schwander B, Lee VH. Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients in Hong Kong. Hong Kong Med J 2014;20:178-86.

2. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29:2866-74. CrossRef

3. Zhou C, Wu YL, Liu X, et al. Overall survival (OS) results from OPTIMAL (CTONG0802), a phase III trial of erlotinib (E) versus carboplatin plus gemcitabine (GC) as first-line treatment for Chinese patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol 2012;30(Suppl);abstract 7520.

4. Lam KC, Mok TS. Comparison is beyond IPASS and OPTIMAL. Hong Kong Med J 2014;20:176-7. CrossRef

5. Shi Y, Zhang L, Liu X, et al. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol 2013;14:953-61. CrossRef

To the Editor—I read with interest the case report published by Shea and Ip titled “Pulmonary tuberculosis complicating asbestosis”.1 On reading the details, I could not agree on the authors’ interpretation of the findings and the diagnosis of asbestosis. While it is beyond doubt that the findings of calcified pleural plaques point towards the diagnosis of a form of “asbestos-related pleural disease”, this condition has to be distinguished from ‘asbestosis’ although the two conditions may co-exist in some patients. Asbestosis refers to scarring of the lung parenchyma as a result of heavy asbestos exposure. Radiological features are usually in the form of reticulation, linear and curvilinear opacities, and parenchymal bands.2 These features were not obvious in the computed tomographic images shown. Rather, the prominent radiological findings were those of fine nodules which, in my view, were more compatible with a diagnosis of ‘cryptic miliary tuberculosis’. Cryptic miliary tuberculosis is a form of tuberculosis which tends to occur in the elderly and presents with fever of unknown origin with negative bacteriological findings.3 Diagnosis is difficult and often delayed. Given the clinical and radiological features of the case reported here, I think a more appropriate title would be “Cryptic miliary tuberculosis in an elderly patient with underlying asbestos-related pleural plaques”.

1. Shea YF, Ip JJ. Pulmonary tuberculosis complicating asbestosis. Hong Kong Med J 2014;20:265.e3-5. CrossRef

2. Roach HD, Davies GJ, Attanoos R, Crane M, Adams H, Phillips S. Asbestos: when the dust settles an imaging review of asbestos-related disease. Radiographics 2002;22:S167-84. CrossRef

3. Yu YL, Chow WH, Humphries MJ, Wong RW, Gabriel M. Cryptic miliary tuberculosis. Q J Med 1986;59:421-8.

To the Editor—We would like to thank Dr CF Wong for clarifying the terminologies used in our article.1 We apologise for not annotating the interstitial septal thickening in the original figures; furthermore, the resolution and greyscale of the images were not optimal to demonstrate the reticulations in our case. We have retrieved one of the baseline computed tomography (CT) images of the thorax of our patient to further demonstrate the presence of interstitial septal thickening on top of the calcified pleural plaques (Fig). These findings signify that our patient had lung parenchymal changes due to asbestos exposure, together with asbestos-related pleural plaques.2 Because of these parenchymal changes, the diagnosis of tuberculosis was challenging in the initial stage. We agree that ‘cryptic pulmonary tuberculosis’ is more specific than ‘pulmonary tuberculosis’ as the final diagnosis for our patient who presented with pyrexia of unknown origin but with apparently negative mycobacterial workup at the beginning while the interval CT thorax showed miliary shadows.3 Perhaps, ‘Cryptic miliary tuberculosis in an elderly patient with asbestosis’ would be an even more accurate and attractive title for this article. We would once again like to thank Dr Wong for sharing his ideas and experience with us.

1. Shea YF, Ip JJ. Pulmonary tuberculosis complicating asbestosis. Hong Kong Med J 2014;20:265.e3-5. CrossRef

2. Fishwick D, Barber CM. Non-malignant asbestos-related diseases: a clinical view. Clin Med 2014;14:68-71. CrossRef

3. Yu YL, Chow WH, Humphries MJ, Wong RW, Gabriel M. Cryptic miliary tuberculosis. Q J Med 1986;59:421-8.

No abstract available.

No abstract available.