The
n e w e ng l a n d j o u r na l
of
m e dic i n e
c or r e sp ondence
First-Line Crizotinib in ALK-Positive Lung Cancer To the Editor: Solomon and colleagues (Dec. 4 issue)1 suggest that, as compared with platinum– pemetrexed chemotherapy, crizotinib treatment was associated with significantly longer progression-free survival and an improved objective response rate. However, the interpretation of these results needs some consideration. In the study, platinum–pemetrexed chemotherapy was used every 3 weeks for up to six cycles. However, pemetrexed was not continued beyond the planned six cycles of the combination chemotherapy. The phase 3 PARAMOUNT trial2 suggested that maintenance therapy with pemetrexed after four cycles of combined cisplatin–pemetrexed therapy resulted in a significant reduction of 22% in the risk of death and in an improvement of almost 3 months in median overall survival. Also, in the PARAMOUNT study,3 maintenance therapy with pemetrexed was associated with improved progression-free survival among patients without disease progression after four cycles. The fact that pemetrexed was not continued beyond the planned chemotherapy may have influenced the outcome of the study by Solomon et al. Deniz Tural, M.D.
plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 2012;13:247-55. DOI: 10.1056/NEJMc1415973
To the Editor: In the study by Solomon et al., important points regarding patients with brain metastases and the toxicity of the regimen caught our attention. First, brain metastasis is an important feature of lung adenocarcinoma. The poor penetration of crizotinib through the blood– brain barrier made it less effective in this subgroup of patients than in the subgroup of patients without brain metastases. Nearly half the patients with brain metastases (which were present in 27% of the patients in the study) had disease progression. Second, crizotinib has a generally good safety profile. However, in most studies in the literature, visual problems are the most commonly reported side effects of the drug. The evaluation of patients with visual disturbances during crizotinib treatment did not show any specific objective ophthalmologic changes.1 Details of the
Akdeniz University Medical School Antalya, Turkey [email protected]
this week’s letters
Saadettin Kilickap, M.D. Hacettepe University Cancer Institute Ankara, Turkey No potential conflict of interest relevant to this letter was reported. 1. Solomon BJ, Mok T, Kim D-W, et al. First-line crizotinib
versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371:2167-77. 2. Paz-Ares LG, de Marinis F, Dediu M, et al. PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013;31:2895-902. 3. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo
781
First-Line Crizotinib in ALK-Positive Lung Cancer
783
Genetic Basis for Clinical Response to CTLA-4 Blockade
784
Conduct Disorder and Callous–Unemotional Traits in Youth
784
Sensor Technology in Assessments of Clinical Skill
786
Viremic Relapse after HIV-1 Remission in a Perinatally Infected Child
n engl j med 372;8 nejm.org february 19, 2015
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF SUSSEX on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
781
The
n e w e ng l a n d j o u r na l
ophthalmologic examinations of the patients with vision disorders could be informative. Ali Alkan, M.D. Elif B. Köksoy, M.D. Güngör Utkan, M.D. Ankara University School of Medicine Ankara, Turkey [email protected] No potential conflict of interest relevant to this letter was reported. 1. Besse B, Salgia R, Bolomon B, et al. Visual disturbances in
patients (pts) with anaplastic lymphoma kinase (alk)-positive advanced non-small cell lung cancer (nsclc) treated with crizotinib. Presented at the 37th Congress of the European Society of Medical Oncology, Vienna, September 28–October 2, 2012. abstract. DOI: 10.1056/NEJMc1415973
of
m e dic i n e
was associated with improved progression-free survival, as compared with chemotherapy, both among patients with brain metastases (hazard ratio, 0.57; 95% confidence interval [CI], 0.35 to 0.93; one-sided P = 0.01) and among those without brain metastases (hazard ratio, 0.46; 95% CI, 0.34 to 0.63; one-sided P
n e w e ng l a n d j o u r na l
of
m e dic i n e
c or r e sp ondence
First-Line Crizotinib in ALK-Positive Lung Cancer To the Editor: Solomon and colleagues (Dec. 4 issue)1 suggest that, as compared with platinum– pemetrexed chemotherapy, crizotinib treatment was associated with significantly longer progression-free survival and an improved objective response rate. However, the interpretation of these results needs some consideration. In the study, platinum–pemetrexed chemotherapy was used every 3 weeks for up to six cycles. However, pemetrexed was not continued beyond the planned six cycles of the combination chemotherapy. The phase 3 PARAMOUNT trial2 suggested that maintenance therapy with pemetrexed after four cycles of combined cisplatin–pemetrexed therapy resulted in a significant reduction of 22% in the risk of death and in an improvement of almost 3 months in median overall survival. Also, in the PARAMOUNT study,3 maintenance therapy with pemetrexed was associated with improved progression-free survival among patients without disease progression after four cycles. The fact that pemetrexed was not continued beyond the planned chemotherapy may have influenced the outcome of the study by Solomon et al. Deniz Tural, M.D.
plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 2012;13:247-55. DOI: 10.1056/NEJMc1415973
To the Editor: In the study by Solomon et al., important points regarding patients with brain metastases and the toxicity of the regimen caught our attention. First, brain metastasis is an important feature of lung adenocarcinoma. The poor penetration of crizotinib through the blood– brain barrier made it less effective in this subgroup of patients than in the subgroup of patients without brain metastases. Nearly half the patients with brain metastases (which were present in 27% of the patients in the study) had disease progression. Second, crizotinib has a generally good safety profile. However, in most studies in the literature, visual problems are the most commonly reported side effects of the drug. The evaluation of patients with visual disturbances during crizotinib treatment did not show any specific objective ophthalmologic changes.1 Details of the
Akdeniz University Medical School Antalya, Turkey [email protected]
this week’s letters
Saadettin Kilickap, M.D. Hacettepe University Cancer Institute Ankara, Turkey No potential conflict of interest relevant to this letter was reported. 1. Solomon BJ, Mok T, Kim D-W, et al. First-line crizotinib
versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371:2167-77. 2. Paz-Ares LG, de Marinis F, Dediu M, et al. PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013;31:2895-902. 3. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo
781
First-Line Crizotinib in ALK-Positive Lung Cancer
783
Genetic Basis for Clinical Response to CTLA-4 Blockade
784
Conduct Disorder and Callous–Unemotional Traits in Youth
784
Sensor Technology in Assessments of Clinical Skill
786
Viremic Relapse after HIV-1 Remission in a Perinatally Infected Child
n engl j med 372;8 nejm.org february 19, 2015
The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF SUSSEX on August 11, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
781
The
n e w e ng l a n d j o u r na l
ophthalmologic examinations of the patients with vision disorders could be informative. Ali Alkan, M.D. Elif B. Köksoy, M.D. Güngör Utkan, M.D. Ankara University School of Medicine Ankara, Turkey [email protected] No potential conflict of interest relevant to this letter was reported. 1. Besse B, Salgia R, Bolomon B, et al. Visual disturbances in
patients (pts) with anaplastic lymphoma kinase (alk)-positive advanced non-small cell lung cancer (nsclc) treated with crizotinib. Presented at the 37th Congress of the European Society of Medical Oncology, Vienna, September 28–October 2, 2012. abstract. DOI: 10.1056/NEJMc1415973
of
m e dic i n e
was associated with improved progression-free survival, as compared with chemotherapy, both among patients with brain metastases (hazard ratio, 0.57; 95% confidence interval [CI], 0.35 to 0.93; one-sided P = 0.01) and among those without brain metastases (hazard ratio, 0.46; 95% CI, 0.34 to 0.63; one-sided P
