Abstract
Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.
| Original language | English (US) |
|---|---|
| Journal | JAMA oncology |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma : Phase 1b Results from the JAVELIN Solid Tumor Trial. / Hassan, Raffit; Thomas, Anish; Nemunaitis, John J.; Patel, Manish R.; Bennouna, Jaafar; Chen, Franklin L.; Delord, Jean Pierre; Dowlati, Afshin; Kochuparambil, Samith T.; Taylor, Matthew; Powderly, John D.; Vaishampayan, Ulka N.; Verschraegen, Claire; Grote, Hans Juergen; Von Heydebreck, Anja; Chin, Kevin; Gulley, James L.
In: JAMA oncology, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy and Safety of Avelumab Treatment in Patients with Advanced Unresectable Mesothelioma
T2 - Phase 1b Results from the JAVELIN Solid Tumor Trial
AU - Hassan, Raffit
AU - Thomas, Anish
AU - Nemunaitis, John J.
AU - Patel, Manish R.
AU - Bennouna, Jaafar
AU - Chen, Franklin L.
AU - Delord, Jean Pierre
AU - Dowlati, Afshin
AU - Kochuparambil, Samith T.
AU - Taylor, Matthew
AU - Powderly, John D.
AU - Vaishampayan, Ulka N.
AU - Verschraegen, Claire
AU - Grote, Hans Juergen
AU - Von Heydebreck, Anja
AU - Chin, Kevin
AU - Gulley, James L.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.
AB - Importance: Patients with malignant mesothelioma whose disease has progressed after platinum and pemetrexed treatment have limited options. Anti-programmed cell death 1 (PD-1) antibodies have antitumor activity in this disease, but little is known about the activity of anti-programmed cell death ligand 1 (PD-L1) antibodies in patients with mesothelioma. Objective: To assess the efficacy and safety of avelumab in a cohort of patients with previously treated mesothelioma. Design, Setting, and Participants: Phase 1b open-label study (JAVELIN Solid Tumor) in patients with unresectable mesothelioma that progressed after platinum and pemetrexed treatment, enrolled at 25 sites in 3 countries between September 9, 2014, and July 22, 2015. Interventions: Participants received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. Main Outcomes and Measures: Prespecified end points included confirmed best overall response based on Response Evaluation Criteria In Solid Tumors, version 1.1; duration of response; progression-free survival (PFS); overall survival (OS); PD-L1 expression-based analyses; and safety. Results: Of 53 patients treated with avelumab, the median age was 67 (range, 32-84) years; 32 (60%) were male. As of December 31, 2016, median follow-up was 24.8 (range, 16.8-27.8) months. Twenty patients (38%) had 3 or more previous lines of therapy (median, 2; range, 1-8). The confirmed objective response rate (ORR) was 9% (5 patients; 95% CI, 3.1%-20.7%), with complete response in 1 patient and partial response in 4 patients. Responses were durable (median, 15.2 months; 95% CI, 11.1 to not estimable months) and occurred in patients with PD-L1-positive tumors (3 of 16; ORR, 19%; 95% CI, 4.0%-45.6%) and PD-L1-negative tumors (2 of 27; ORR, 7%; 95% CI, 0.9%-24.3%) based on a 5% or greater PD-L1 cutoff. Disease control rate was 58% (31 patients). Median PFS was 4.1 (95% CI, 1.4-6.2) months, and the 12-month PFS rate was 17.4% (95% CI, 7.7%-30.4%). Median OS was 10.7 (95% CI, 6.4-20.2) months, and the median 12-month OS rate was 43.8% (95% CI, 29.8%-57.0%). Five patients (9%) had a grade 3 or 4 treatment-related adverse event, and 3 (6%) had a grade 3 or 4 immune-related, treatment-related adverse event. There were no treatment-related deaths. Conclusions and Relevance: Avelumab showed durable antitumor activity and disease control with an acceptable safety profile in a heavily pretreated cohort of patients with mesothelioma. Trial Registration: ClinicalTrials.gov identifier: NCT01772004.
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UR - http://www.scopus.com/inward/citedby.url?scp=85059642176&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2018.5428
DO - 10.1001/jamaoncol.2018.5428
M3 - Article
C2 - 30605211
AN - SCOPUS:85059642176
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
ER -