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Table of Contents
LETTER TO EDITOR
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 266-267

Desperate times, desperate measures: Low-dose nivolumab-induced remission in relapsed NSCLC


Department of Medical Oncology, Tata Memorial Centre, HBNI, Mumbai, Maharashtra, India

Date of Web Publication20-Dec-2019

Correspondence Address:
Kumar Prabhash
Department of Medical Oncology, Tata Memorial Centre, HBNI, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_82_19

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How to cite this article:
Talreja VT, Noronha V, Patil VM, Joshi A, Prabhash K. Desperate times, desperate measures: Low-dose nivolumab-induced remission in relapsed NSCLC. Cancer Res Stat Treat 2019;2:266-7

How to cite this URL:
Talreja VT, Noronha V, Patil VM, Joshi A, Prabhash K. Desperate times, desperate measures: Low-dose nivolumab-induced remission in relapsed NSCLC. Cancer Res Stat Treat [serial online] 2019 [cited 2020 Apr 3];2:266-7. Available from: http://www.crstonline.com/text.asp?2019/2/2/266/273698



Immunotherapy with checkpoint inhibitors has become a common treatment option for a variety of cancers. Pembrolizumab (anti-programmed death [PD]-1 antibody) and nivolumab (anti-PD-ligand 1 [PD-L1]) are both approved by the Food and Drug Administration (FDA) for use in metastatic non-small cell lung carcinoma (NSCLC).[1] Data from Phase I studies that used multiple-dose levels suggest that in general, response does not decrease with decrease in doses.[2],[3],[4],[5],[6] The dose–response curve does not seem to be linear in immunotherapy. In a retrospective analysis published by Yoo et al. from Korea, low-dose immunotherapy with nivolumab appeared to be as effective as standard dose.[7] The objective response rate was 16.7% in the low-dose group as compared to 13.8% in the standard-dose group (P = 0.788) at a median follow-up of 5.2 months. The median overall survival in all the patients in the study was 12.5 months; 8.2 months in the patients treated with standard-dose nivolumab and 12.5 months in those treated with low-dose nivolumab, thus making a strong case for exploring low-dose nivolumab. The biomarker PD-L1 immunohistochemistry (IHC) assays vary with four FDA-approved antibodies (22C3, 28-8, SP263, and SP142) and two platforms (Dako and Ventana), each with their own scoring system.[8] While PD-L1 expression might be used as a surrogate biomarker for benefit in nonsquamous NSCLC, as shown in Checkmate 017 and Checkmate 057 trials, in squamous cell NSCLC, it is neither predictive nor prognostic.[9] In the retrospective analysis by Yoo et al. on the use of low-dose immunotherapy, they found that neither the dose of nivolumab nor the PD-L1 level correlated with survival.[7]

We present a case of a patient with metastatic NSCLC who had progressed on three lines of chemotherapy and had limited financial resources who had a good response to low-dose nivolumab. A 45-year-old male never-smoker presented with left-sided neck swelling in September 2017. Imaging revealed a right upper lobe lung mass, right hilar and mediastinal lymphadenopathy, bilateral cervical lymphadenopathy, and brain lesions (multiple ring-enhancing lesions with perilesional edema in the right parietal, right temporal, and left occipital lobe). Biopsy of the left supraclavicular lymph node revealed NSCLC, thyroid transcription factor-1 positive, and p40 negative consistent with metastatic adenocarcinoma of primary pulmonary origin. The tumor was negative for ALK1 on IHC, and epidermal growth factor receptor mutation analysis by real-time polymerase chain reaction was also negative. Testing for PD-L1 was not performed.

He received whole-brain radiotherapy, followed by four cycles of carboplatin and pemetrexed. Tumor restaging revealed a partial response, and he was continued on four cycles of maintenance pemetrexed. The patient developed progressive disease in June 2018 and received single-agent gemcitabine, but restaging after three cycles revealed progressive disease. The patient then received 24 cycles of weekly paclitaxel with partial remission as the best response. In May 2019, he was admitted to the hospital with progressive cough, dyspnea, and chest pain, and restaging revealed progressive disease with increase in the size of the right upper lobe lung lesion and subcarinal lymph node [Figure 1]a and [Figure 1]c. His Eastern Cooperative Oncology Group performance status was 2.
Figure 1: Contrast-enhanced computed tomography scan imaging of the patient at baseline (May 2019) showing right upper lobe lung mass (a) and subcarinal lymphadenopathy (c) and in October 2019 which are post-low-dose nivolumab scans showing response in the lung mass (b) and subcarinal lymphadenopathy (d)

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After discussion of the standard therapeutic options and non affordability of the standard dose of nivolumab, he was started on nivolumab 40 mg in May 2019. After the first cycle, he felt much better with improvement in his symptoms. He continued on nivolumab 40 mg intravenously every 2 weeks and received a total of 12 cycles until the last follow-up in October 2019. Restaging scans in October 2019 [Figure 1]b and d] showed complete resolution of the 2.6 cm × 1.4 cm mass in the right upper lobe and decrease in size of mediastinal and right hilar nodes, largest in the subcarinal region which now measured 15 mm × 13 mm as compared to 35 mm × 28 mm in May 2019. In terms of toxicity, he developed Grade 2 hypothyroidism (October 2019: serum thyroid-stimulating hormone [TSH] >100 μIU/ml, serum T4: 0.91 μg/dl, serum T3: 0.27 ng/ml; baseline thyroid function tests in May 2019 were normal with serum TSH: 1.38 μIU/ml, serum T4: 8.64 μg/dl, and serum T3: 0.75 ng/ml) requiring oral thyroxine supplementation.

In conclusion, our case is an example of a response to low-dose immunotherapy in a patient who was running out of options after failing multiple chemotherapy regimens with limited resources. Further clinical studies to validate this finding are the need of the hour, and it would be important to explore the dose–response of immunotherapy in different histology tumors and in other malignancies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Feng Y, Wang X, Bajaj G, Agrawal S, Bello A, Lestini B, et al. Nivolumab exposure-response analyses of efficacy and safety in previously treated squamous or nonsquamous non-small cell lung cancer. Clin Cancer Res 2017;23:5394-405.  Back to cited text no. 2
    
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Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167-75.  Back to cited text no. 3
    
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Agrawal S, Feng Y, Roy A, Kollia G, Lestini B. Nivolumab dose selection: Challenges, opportunities and lessons learned for cancer immunotherapy. J Immunother Cancer 2015;3 Suppl 2:141.  Back to cited text no. 4
    
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Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in patients with advanced solid tumors. Clin Cancer Res 2015;21:4286-93.  Back to cited text no. 5
    
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Patil VM, Noronha V, Joshi A, Abhyankar A, Menon N, Banavali S, et al. Low doses in immunotherapy: Are they effective? Cancer Res Stat Treat 2019;2:54-60.  Back to cited text no. 6
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Yoo SH, Keam B, Kim M, Kim SH, Kim YJ, Kim TM, et al. Low-dose nivolumab can be effective in non-small cell lung cancer: Alternative option for financial toxicity. ESMO Open 2018;3:e000332.  Back to cited text no. 7
    
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Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 2014;20:5064-74.  Back to cited text no. 8
    
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Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015;373:123-35.  Back to cited text no. 9
    


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