Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial

Autor: James L. Gulley, Kevin M. Chin, Ding Wang, Anja von Heydebreck, Hans Juergen Grote, David R. Spigel, Joseph Leach, Jason C. Chandler, Jean Marie Cuillerot, Deborah J.L. Wong, Nicholas Iannotti, W. Jeff Edenfield, Karen Kelly, Arun Rajan
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Lung Neoplasms
Drug Resistance
Platinum Compounds
Avelumab
Pulmonary Disease
Chronic Obstructive
0302 clinical medicine
Carcinoma
Non-Small-Cell Lung
Monoclonal
Infusions
Intravenous
Non-Small-Cell Lung
Fatigue
Antibodies
Monoclonal
Nausea
Middle Aged
Editorial
Oncology
Tolerability
Local
Response Evaluation Criteria in Solid Tumors
030220 oncology & carcinogenesis
Cohort
Retreatment
Disease Progression
Female
Intravenous
medicine.drug
medicine.medical_specialty
Chronic Obstructive
Infusions
Oncology and Carcinogenesis
Antineoplastic Agents
Antibodies
Monoclonal
Humanized
Article
Antibodies
Pulmonary Disease
03 medical and health sciences
Internal medicine
Carcinoma
medicine
Humans
Oncology & Carcinogenesis
Adverse effect
Lung cancer
Aged
business.industry
Pneumonia
Lipase
medicine.disease
Surgery
Clinical trial
030104 developmental biology
Neoplasm Recurrence
Dyspnea
Drug Resistance
Neoplasm
Neoplasm
Neoplasm Recurrence
Local
business
Zdroj: The Lancet. Oncology, vol 18, iss 5
Gulley, JL; Rajan, A; Spigel, DR; Iannotti, N; Chandler, J; Wong, DJL; et al.(2017). Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. The Lancet Oncology, 18(5), 599-610. doi: 10.1016/S1470-2045(17)30240-1. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/4x88f141
Popis: Summary Background Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). Methods In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing. Findings Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2–11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8–18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression. Interpretation Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Funding Merck KGaA and Pfizer.
Databáze: OpenAIRE
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