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CASE REPORT
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Successful treatment with durvalumab: A case report and review


 Hospital Pharmacy, Unidad de Gestión Clínica Farmacia, Hospital Juan Ramón Jiménez, Huelva, Spain

Date of Submission23-Aug-2021
Date of Decision09-Oct-2021
Date of Web Publication24-Nov-2021

Correspondence Address:
Ana Peláez Bejarano,
Unidad de Gestión Clínica Farmacia, Hospital Juan Ramón Jiménez, Ronda Norte S/N, 21005 Huelva
Spain
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_1430_21

 > Abstract 


Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of disease entities with multimodality treatments. For most patients, platinum-based doublet with concurrent chemoradiotherapy (CRT) has become the first-choice treatment over the past decade. Immune checkpoint inhibition has revolutionized the management of metastatic NSCLC; however, no major advances in systemic therapy for Stage III NSCLC have been made. The following report is the case of a patient with unresectable Stage IIIA NSCLC successfully treated with durvalumab. The patient completed 1 year of treatment without interruptions, and disease control has been maintained for more than 20 months since the start of durvalumab.

Keywords: Antiprogrammed cell death ligand 1, consolidation, durvalumab, immunotherapy, non-small-cell lung cancer



How to cite this URL:
Bejarano AP, Pérez OM. Successful treatment with durvalumab: A case report and review. J Can Res Ther [Epub ahead of print] [cited 2021 Nov 28]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=331104




 > Introduction Top


Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of disease entities with multimodality treatments involving radiotherapy, chemotherapy, and surgical resection.[1] For most patients, platinum-based doublet with concurrent chemoradiotherapy (CRT) has become the first-choice treatment over the past decade.[2] Patient prognosis with this treatment is poor, with 5-year survival rates of approximately 15%–30%.[3]

Immune checkpoint inhibition (ICI) has revolutionized the management of metastatic NSCLC; however, no major advances in systemic therapy for Stage III NSCLC have been made.[4]

Durvalumab is a fully human immunoglobulin G1 kappa antibody targeting programmed cell death ligand 1 (PD-L1).[5] In the PACIFIC clinical trial, durvalumab showed durable efficacy and well tolerance in patients with Stage III unresectable NSCLC without disease progression after CRT.[6]

The following report is the case of a patient with unresectable Stage IIIA NSCLC successfully treated with durvalumab.


 > Case Report Top


The patient was a 64-year-old male who presented to the emergency room with dry cough, dyspnea, and weight loss. He has been a smoker of 35 packs/year for the last 30 years. Medical history included obstructive sleep apnea and permanent atrial fibrillation.

Positron emission tomography detected a mass measuring approximately 2 cm × 4.7 cm × 1.5 cm (height, long, and width) in the lower left lobe of the lung. No distant metastases were observed. Histology revealed adenocarcinoma, and subsequent imaging established a diagnosis of unresectable Stage IIIA NSCLC (T2bN2M0).[7] Epidermal growth factor receptor gene mutations and the anaplastic lymphoma kinase gene were not detected. The expression level of PD-L1 was >1% (determination through VENTANA PD-L1 SP263 platform).

Due to his unresectable disease, the patient was candidate for concurrent CRT. Chemotherapy with cisplatin and vinorelbine was performed, and concurrent radiotherapy (fractionated radiotherapy to 60 Gy in 2 Gy daily fractions) was started. Four cycles of chemotherapy and thirty cycles of radiotherapy were completed. The following concurrent CRT-related toxicities were reported: esophagitis (Grade 2), nausea (Grade 2), and oral mucositis (Grade 2), based on the Common Terminology Criteria for Adverse Events.[8] After completion of concurrent CRT, a computed tomography (CT) was performed. The patient showed good tolerance and reached partial response.

Then, once nonprogressive disease was confirmed, it was decided to start treatment with durvalumab as consolidation therapy. Contraindications (autoimmune disease and transplantation) and latent infections (human immunodeficiency virus, Hepatitis B, Hepatitis C, and tuberculosis) were ruled out. Durvalumab was initiated 14 weeks after completion of concurrent CRT. The patient was prescribed durvalumab 10 mg/kg (total dose 740 mg) every 14 days. Stable response was confirmed after six cycles by chest CT. Radiation bronchiectasis occurred 20 weeks after completion of concurrent CRT, but the patient remained asymptomatic. The patient underwent imaging studies every 2 months. Pulmonary lesions were evaluated confirming nonprogressive disease and marked decrease in the primary lesion [Figure 1]. Periodically, to rule out the immune-mediated adverse events, thyroid hormones (thyroiditis) and serum creatinine (nephritis) determinations were performed. In addition, chest CT scans were also performed to detect pneumonitis. There were no immune-mediated adverse events throughout the treatment with durvalumab.
Figure 1: Radiologic imaging: Chest computed tomography scan at baseline showing a solid mass growing into the lumen of the left main bronchus causing obstruction of the left main bronchus and obstructive atelectasis of the left lower lobe (left). To the right, 6 months after durvalumab treatment with marked decrease in the size of the left hilar mass and disappearance of postobstructive consolidation of the left lower lobe (right)

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Periodically, to rule out the immune-mediated adverse events, thyroid hormone (thyroiditis) and serum creatinine (nephritis) determinations were performed. In addition, chest CT scans were also performed to detect pneumonitis.

The patient completed 1 year of treatment with durvalumab without interruptions, and disease control has been maintained for more than 20 months since the start of immunotherapy durvalumab treatment. No recurrence or metastasis was observed.


 > Discussion Top


The poor long-term survival for unresectable Stage III NSCLC patients, as a result of the subsequent progression and metastasis of the residual disease following definitive chemoradiation, has been a major challenge that demands an effective consolidation treatment.[9] Management of Stage III NSCLC changed with the results from the PACIFIC trial and following worldwide health authority approvals of durvalumab.[10]

The consolidation treatment for the Stage III unresectable NSCLC patients has been a controversial practice mainly due to the tolerability secondary to the side effects of concurrent CRT. The time window between the end of CRT and the start of durvalumab can be crucial, as patients may experience disease progression in this period without treatment.[1] In this case, our patient received the first cycle of durvalumab 14 weeks after finishing concurrent CRT. Although the patient reported some adverse events during (esophagitis, nausea, and oral mucositis) and after (bronchiectasis) concurrent CRT, they could be managed.

In this context, a review of the literature related to the use of durvalumab for patients with NSCLC was carried out, to summarize the available information. An electronic search in PubMed was performed, using the MeSH terms “durvalumab,” “non-small cell lung carcinoma,” and “case reports” without time restrictions, revealing 503 results/items, but only 12 were related to this topic. Case reports were selected, and guidelines, randomized controlled trials, narrative reviews, and systematic reviews/meta-analyses were excluded.

As shown in [Table 1], these publications reported a total of 12 cases (11 males and 1 female) about patients in the age range of 45–79 years old. More than half of the patients (n = 7) received concurrent CRT prior to starting durvalumab. The dosage regimens described for durvalumab were 10 mg/kg every 2 weeks (n = 7), 10 mg/kg every 3 weeks (n = 1), 10 mg/kg every 4 weeks (n = 1), and 20 mg/kg every 4 weeks (n = 1). Type of remission was reported only for five patients (partial response in two patients and complete remission in three patients). Treatment duration was variable, with a range of 2–24 months.
Table 1: Results of the review of patients with non-small-cell lung cancer who received durvalumab

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Regarding outcomes, five patients had stable disease, three patients reported progression during treatment, one patient died due to an adverse event from durvalumab, and there was no information regarding the other 3. Finally, adverse events due to durvalumab were reported in almost every case, with the exception of four cases where successful treatment with durvalumab was reported. Probably, because this drug has only recently been marketed, there are not many articles reporting treatments in daily practice.

Some authors stand by the opinion that the next step in the use of ICI for patients with lung cancer is to start the treatment on an earlier-stage disease. Many clinical trials are being carried out to prove whether there is benefit in providing ICI treatment in either the adjuvant or neoadjuvant setting.[4] However, in these early stages, the use of immunotherapy has a different purpose because the aim of the treatment is to cure the disease, and therefore, the objectives formulated in the clinical trials are different.[22]

Immuno-oncology has become one of the pillars of lung cancer treatment and will likely be the paradigm of therapeutic innovation for years to come.[4]


 > Conclusion Top


This case reported a successful treatment with durvalumab monotherapy as consolidation therapy for unresectable Stage IIIA NSCLC and achieved sustained stable response for more than 20 months.

Consent for patient consent

Informed consent was obtained from the patient for the publication of the case report.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Chu CH, Chiu TH, Wang CC, Chang WC, Huang AC, Liu CY, et al. Consolidation treatment of durvalumab after chemoradiation in real-world patients with stage III unresectable non-small cell lung cancer. Thorac Cancer 2020;11:1541-9.  Back to cited text no. 1
    
2.
Botticella A, Mezquita L, Le Pechoux C, Planchard D. Durvalumab for stage III non-small-cell lung cancer patients: Clinical evidence and real-world experience. Ther Adv Respir Dis 2019;13:1753466619885530.  Back to cited text no. 2
    
3.
Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol 2017;8:1-20.  Back to cited text no. 3
    
4.
Dawe DE, Harlos CH, Juergens RA. Immuno-oncology-the new paradigm of lung cancer treatment. Curr Oncol 2020;27:S78-86.  Back to cited text no. 4
    
5.
Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, et al. Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer Immunol Res 2015;3:1052-62.  Back to cited text no. 5
    
6.
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017;377:1919-29.  Back to cited text no. 6
    
7.
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67:93-9.  Back to cited text no. 7
    
8.
Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Published: November, 27. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2020.  Back to cited text no. 8
    
9.
Chen W, Zhang H, Huang W, Lan T. A case report of sustained clinical remission in patients with locally advanced lung adenocarcinoma after sequential immunotherapy following concurrent chemoradiotherapy. Ann Palliat Med 2020;9:4346-52.  Back to cited text no. 9
    
10.
Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC-update from PACIFIC. J Thorac Oncol 2020;15:288-93.  Back to cited text no. 10
    
11.
Gupta A, Tun A, Ticona K, Baqui A, Guevara E. Invasive aspergillosis in a patient with stage III (or 3a or 3b) non-small-cell lung cancer treated with durvalumab. Case Rep Oncol Med 2019;2019:2178925.  Back to cited text no. 11
    
12.
Sumi T, Ikeda T, Kure K, Yamada Y, Nakata H, Mori Y. Bronchomediastinal fistula during durvalumab therapy after chemoradiotherapy in stage III NSCLC. J Thorac Oncol 2019;14:1860-1.  Back to cited text no. 12
    
13.
Andrade AR, Moll-Udina A, Martin R, Cilveti E, Subirà O, Disfetano L, et al. Retinal vasculitis secondary to durvalumab. Case Rep Ophthalmol 2020;11:161-6.  Back to cited text no. 13
    
14.
Yorozuya T, Taya T, Yasuda K, Nagano Y, Shioya M, Chiba H, et al. Long-term response with durvalumab after chemoradiotherapy for pulmonary pleomorphic carcinoma: A case report. Thorac Cancer 2020;11:1090-3.  Back to cited text no. 14
    
15.
Taima K, Tanaka H, Itoga M, Ishioka Y, Kurose A, Tasaka S. Destroyed lung due to sustained inflammation after chemoradiotherapy followed by durvalumab. Respirol Case Rep 2020;8:e00580.  Back to cited text no. 15
    
16.
Kanaoka K, Ikebe S, Ihara S, Tsuji H, Yasuoka H, Minami S. Durvalumab-induced diffuse alveolar hemorrhage: An autopsy case report. Case Rep Oncol 2020;13:696-701.  Back to cited text no. 16
    
17.
Nakamura M, Otsuka T, Hayashi R, Horita T, Ota M, Sakurai N, et al. Durvalumab-induced immune-related hepatitis in a patient with non-small cell lung cancer. Intern Med 2020;59:2711-7.  Back to cited text no. 17
    
18.
Kawai S, Suzuki H, Okuma Y. Durvalumab consolidation treatment after chemoradiotherapy for an HIV-positive patient with locally advanced non-small cell lung cancer. Case Rep Oncol 2020;13:747-53.  Back to cited text no. 18
    
19.
Tao H, Li F, Li R, Han X, Hu Y. Successful treatment of a patient with non-small cell lung cancer and interstitial lung disease with durvalumab: A case report. Ann Palliat Med 2020;9:3623-8.  Back to cited text no. 19
    
20.
Zhang T, Wu Y, Zheng S, Cheng G, He X, Bi N. Durvalumab after concurrent chemoradiotherapy in a patient with chemotherapy-resistant unresectable stage III non-small cell lung cancer: A case report. Ann Palliat Med 2020;9:2375-80.  Back to cited text no. 20
    
21.
Manko S, Côté B, Provost N. A case of durvalumab-induced lichenoid eruption evolving to bullous eruption after phototherapy: A case report. SAGE Open Med Case Rep 2021;9:2050313X21993279.  Back to cited text no. 21
    
22.
Mielgo-Rubio X, Calvo V, Luna J, Remon J, Martín M, Berraondo P, et al. Immunotherapy moves to the early-stage setting in non-small cell lung cancer: Emerging evidence and the role of biomarkers. Cancers (Basel) 2020;12:3459.  Back to cited text no. 22
    


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