Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial

The Lancet Oncology

Volumn 18, Issue 5, 2017, Pages 623-630

  Alley, Evan W ^a   Lopez, Juanita ^b   Santoro, Armando ^c   Morosky, Anne ^d   Saraf, Sanatan ^d   Piperdi, Bilal ^d   van Brummelen, Emilie ^e  

^a PENN PRESBYTERIAN MEDICAL CENTER   (United States)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^d MERCK RESEARCH LABORATORIES   (United States)

^e NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; GAMMA GLUTAMYLTRANSFERASE; HEMOGLOBIN; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; ANTINEOPLASTIC AGENT; CD274 PROTEIN, HUMAN; MONOCLONAL ANTIBODY;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; ASTHENIA; BALANCE DISORDER; BURNING SENSATION; CANCER PAIN; CLINICAL ARTICLE; CONSTIPATION; COUGHING; DECREASED APPETITE; DIARRHEA; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRY SKIN; DYSGEUSIA; DYSPNEA; ERYTHEMA; ERYTHEMA MULTIFORME; FATIGUE; FEMALE; FEVER; HEADACHE; HUMAN; HYPOCALCEMIA; HYPOTHYROIDISM; IMMUNOHISTOCHEMISTRY; INFUSION RELATED REACTION; IRIDOCYCLITIS; JOINT STIFFNESS; LEUKOCYTE COUNT; MACULOPAPULAR RASH; MALE; MIDDLE AGED; MUCOSA INFLAMMATION; MULTICENTER STUDY; MUSCULOSKELETAL STIFFNESS; MYALGIA; NAUSEA; NEUTROPHIL COUNT; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PARESTHESIA; PHASE 1 CLINICAL TRIAL; PLEURA MESOTHELIOMA; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; RHABDOMYOLYSIS; SIDE EFFECT; THORAX PAIN; THROMBOCYTOPENIA; THROMBOSIS; XEROSTOMIA; CHEMICALLY INDUCED; CHEMISTRY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL (TOPIC); MESOTHELIOMA; PLEURAL NEOPLASMS; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; RETREATMENT;

AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; ARTHRALGIA; FATIGUE; FEMALE; HUMANS; MALE; MESOTHELIOMA; MIDDLE AGED; NAUSEA; NON-RANDOMIZED CONTROLLED TRIALS AS TOPIC; PLEURAL NEOPLASMS; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; RETREATMENT;

EID: 85014866829     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(17)30169-9     Document Type: Article

References (35)

1. 1 Robinson, BM, Malignant pleural mesothelioma: an epidemiological perspective. Ann Cardiothorac Surg 1 (2012), 491–496.
2. 2 Goudar, RK, Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma. Ther Clin Risk Manag 4 (2008), 205–211.
3. 3 Inai, K, Pathology of mesothelioma. Environ Health Prev Med 13 (2008), 60–64.
4. 4 Milano, MT, Zhang, H, Malignant pleural mesothelioma: a population-based study of survival. J Thorac Oncol 5 (2010), 1841–1848.
5. 5 Ettigner, DS, Wood, DE, Akerley, W, et al. NCCN clinical practice guidelines in oncology (NCCN Guidelines): malignant pleural mesothelioma. https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf (accessed Nov 7, 2016).
6. 6 Lilly, Alimta (pemetrexed disodium) injection, powder, lyophilized, for solution for intravenous use, 2016, Lilly, Indianapolis, IN.
7. 7 Vogelzang, NJ, Rusthoven, JJ, Symanowski, J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21 (2003), 2636–2644.
8. 8 Jassem, J, Ramlau, R, Santoro, A, et al. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol 26 (2008), 1698–1704.
9. 9 Ceresoli, GL, Zucali, PA, De, VF, et al. Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma. Lung Cancer 72 (2011), 73–77.
10. 10 Zucali, PA, Simonelli, M, Michetti, G, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer 75 (2012), 360–367.
11. 11 Zucali, PA, Ceresoli, GL, Garassino, I, et al. Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma. Cancer 112 (2008), 1555–1561.
12. 12 Stebbing, J, Powles, T, McPherson, K, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer 63 (2009), 94–97.
13. 13 Okuno, SH, Delaune, R, Sloan, JA, et al. A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma: a North Central Cancer Treatment Study, N0021. Cancer 112 (2008), 1772–1779.
14. 14 Fennell, DA, Steele, JP, Shamash, J, et al. Efficacy and safety of first- or second-line irinotecan, cisplatin, and mitomycin in mesothelioma. Cancer 109 (2007), 93–99.
15. 15 Pardoll, DM, The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12 (2012), 252–264.
16. 16 Sul, J, Blumenthal, GM, Jiang, X, et al. US Food and Drug Administration approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist 21 (2016), 643–650.
17. 17 Reck, M, Rodríguez-Abreu, D, Robinson, AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375 (2016), 1823–1833.
18. 18 Garon, EB, Rizvi, NA, Hui, R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372 (2015), 2018–2028.
19. 19 Herbst, RS, Baas, P, Kim, DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387 (2016), 1540–1550.
20. 20 Cedres, S, Ponce-Aix, S, Zugazagoitia, J, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One, 10, 2015, e0121071.
21. 21 Mansfield, AS, Roden, AC, Peikert, T, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol 9 (2014), 1036–1040.
22. 22 Dolled-Filhart, M, Roach, C, Toland, G, et al. Development of a companion diagnostic for pembrolizumab in non-small cell lung cancer using immunohistochemistry for programmed death ligand-1. Arch Pathol Lab Med 140 (2016), 1243–1249.
23. 23 Dako North American. PD-L1 IHC 22C3 pharmDx, 2015, Dako North America, Carpinteria, CA.
24. 24 Chatterjee, M, Turner, DC, Felip, E, et al. Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann Oncol 27 (2016), 1291–1298.
25. 25 Robert, C, Ribas, A, Wolchok, JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384 (2014), 1109–1117.
26. 26 Hamid, O, Robert, C, Daud, A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369 (2013), 134–144.
27. 27 Robert, C, Joshua, AM, Weber, JS, et al. Pembrolizumab (pembro; MK-3475) for advanced melanoma (MEL): randomized comparison of two dosing schedules. Ann Oncol 25 (2014), 1–41.
28. 28 Krug, LM, Kindler, HL, Calvert, H, et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol 16 (2015), 447–456.
29. 29 Kindler, HL, Scherpereel, A, Calabro, L, et al. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): results from the global, double-blind, placebo-controlled DETERMINE study. Proc Am Soc Clin Oncol, 34(suppl 1), 2016 abstr 8502.
30. 30 Hassan, R, Thomas, A, Patel, MR, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothemoma from the JAVELIN solid tumor phase 1b trial: safety, clinical activity and PD-L1 espression. Proc Am Soc Clin Oncol, 34(suppl 1), 2016 abstr 8503.
31. 31 Calabro, L, Morra, A, Fonsatti, E, et al. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol 14 (2013), 1104–1111.
32. 32 Calabro, L, Morra, A, Fonsatti, E, et al. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med 3 (2015), 301–309.
33. 33 Yano, S, Li, Q, Wang, W, et al. Antiangiogenic therapies for malignant pleural mesothelioma. Front Biosci 16 (2011), 740–748.
34. 34 Zalcman, G, Mazieres, J, Margery, J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 387 (2016), 1405–1414.
35. 35 Freshwater T, Stone J, de Greef R, et al. Assessment of pembrolizumab (MK-3475) dosing strategy based on population pharmacokinetics and exposure-response models. J Immunother Cancer (in press).