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| CASE REPORT |
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| Ahead of print publication |
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Successful treatment with durvalumab: A case report and review
Ana Peláez Bejarano, Olalla Montero Pérez
Hospital Pharmacy, Unidad de Gestión Clínica Farmacia, Hospital Juan Ramón Jiménez, Huelva, Spain
| Date of Submission | 23-Aug-2021 |
| Date of Decision | 09-Oct-2021 |
| Date of Web Publication | 24-Nov-2021 |
Correspondence Address:
Ana Peláez Bejarano,
Unidad de Gestión Clínica Farmacia, Hospital Juan Ramón Jiménez, Ronda Norte S/N, 21005 Huelva
Spain
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jcrt.jcrt_1430_21
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
| > Introduction | |  |
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 | | |
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 | | |
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 | | |
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 | | |
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[Figure 1]
[Table 1]
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