Malignant Pleural Mesothelioma Cancers Treatment Regimens

Malignant Pleural Mesothelioma Cancers Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Induction Chemotherapy1

REGIMEN

DOSING

Pemetrexed/Carboplatin2-7,a,b,d

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks for 6 cycles.

Pemetrexed/Cisplatin
(Category 1)2,7-10,a-c

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks for 4 cycles.

▶Systemic Therapy Regimens1

First-Line Systemic Therapy

Preferred

Nivolumab + Ipilimumab
(Category 1)11-16,e,f

Days 1,22: Nivolumab 360mg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks or up until 2 years of therapy has been completed.

Pemetrexed/Cisplatin
(Category 1)2,7-10,a-c

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours.

Repeat cycle every 3 weeks.

Pemetrexed/Cisplatin + Bevacizumab followed by Bevacizumab maintenance
(Category 1)2,8,17,18,a-e,g

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Cisplatin 75mg/m2 IV over 2 hours

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for 6 cycles followed by maintenance therapy with:

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Other Recommended

Pemetrexed/Carboplatin2-7,a,b,d

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes.

Repeat cycle every 3 weeks.

Pemetrexed/Carboplatin + Bevacizumab followed by Bevacizumab maintenance2,3,7,17,19,a,b,d,e,g

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes, followed by:

Day 1: Carboplatin AUC 5 IV over 30 minutes

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks for 6 cycles followed by maintenance therapy with:

Day 1: Bevacizumab 15mg/kg IV.

Repeat cycle every 3 weeks.

Useful in Certain Circumstances

Gemcitabine/Cisplatin8,20-22,c

Days 1,8,15: Gemcitabine 1,000mg/m2 over 30 minutes, followed by:

Day 1: Cisplatin 100 mg/m2 IV over 2 hours.

Repeat every 4 weeks for a maximum of 6 cycles.

OR

Days 1,8: Gemcitabine 1,250mg/m2 over 30 minutes, followed by:

Day 1: Cisplatin 80 mg/m2 IV over 2 hours.

Repeat every 3 weeks for a maximum of 6 weeks.

Pemetrexed2,23-25,a,b

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Vinorelbine26-29

Day 1: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every week.

OR

Days 1,8,15,22,29,36: Vinorelbine 25-30mg/m2 IV over 5-10 minutes

Repeat cycle every 8 weeks (6 weeks on followed by 2 weeks off treatment).

OR

Days 1,8: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every 3 weeks.

Subsequent Systemic Therapy

Preferred

Nivolumab11-13,30

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Nivolumab + Ipilimumab
(if not administered first-line)11-16,e,f

Day 1: Nivolumab 240mg IV over 30 minutes, with:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks for 4 cycles.

OR

Days 1,15,29: Nivolumab 3mg/kg IV over 30 minutes, followed by:

Day 1: Ipilimumab 1mg/kg IV over 30 minutes.

Repeat cycle every 6 weeks or until up to 2 years of therapy has been completed.

Pembrolizumab31-34

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks or until up to 2 years of therapy has been completed.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 6 weeks or until up to 2 years of therapy has been completed.

Pemetrexed (if not administered first-line; consider rechallenge if good sustained response at the time initial chemotherapy was interrupted) (Category 1)2,23-25,a,b

Day 1: Pemetrexed 500mg/m2 IV over 10 minutes.

Repeat cycle every 3 weeks.

Useful in Certain Circumstances

Gemcitabine20,22,29

Days 1,8,15: Gemcitabine 1,000-1250mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

OR

Days 1,8: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

Vinorelbine26-29

Day 1: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every week.

OR

Days 1,8,15,22,29,36: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every 8 weeks (6 weeks on followed by 2 weeks off treatment).

OR

Days 1,8: Vinorelbine 25-30mg/m2 IV over 5-10 minutes.

Repeat cycle every 3 weeks.

  a Premedication and supplemental medications to reduce the incidence and severity of hematologic, gastrointestinal, and cutaneous toxicities are required for Pemetrexed. The recommended dosing is: vitamin B12 (cyanocobalamin) 1,000mcg IM during the week preceding the first cycle of pemetrexed and every 3 cycles thereafter, and folic acid 400-1,000mcg oral once daily starting 1 week before the first cycle and continuing for 3 weeks after the last dose of pemetrexed, and dexamethasone 4 mg orally twice daily for 3 days starting the day prior to pemetrexed.

  b Pemetrexed-based chemotherapy may also be used for malignant peritoneal mesothelioma, pericardial mesothelioma, and tunica vaginalis testis mesothelioma.

  c Hydration is required with supplemental electrolytes pre- and post-administration of cisplatin.

  d Appropriate for patients not eligible for cisplatin

  e The combination regimens pemetrexed/cisplatin/bevacizumab, pemetrexed/carboplatin/bevacizumab, and nivolumab/ipilimumab are only for unresectable disease.

  f Nivolumab/ipilimumab is preferred for patients with biphasic or sarcomatoid histology and is also an option with epithelioid histology

  g An FDA-approved biosimilar is an appropriate substitute for bevacizumab.

References

1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Malignant Pleural Mesothelioma V.2.2021. Accessed July 5, 2021.

2. Pemetrexed (Alimta) [package insert]. Indianapolis, IN: Lilly USA, LLC; February 2021.

3. Carboplatin [package insert]. Orlando, FL: Ingenus Pharmaceuticals; August 2017.

4. Ceresoli GL, Zucali PA, Favaretto AG, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006;24(9):1443-1448.

5. Castagneto B, Botta M, Aitini E, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008;19(2):370-373.

6. Katirtzoglou N, Gkiozos I, Makrilia N, et al. Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study. Clin Lung Cancer. 2010;11(1):30-35.

7. Santoro A, O’Brien ME, Stahel RA, et al. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol. 2008;3(7):756-763.

8. Cisplatin [package insert]. Paramus, NJ: WG Critical Care LLC; February 2019.

9. 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. 2003;21(14):2636-2644.

10. Krug LM, Pass HI, Rusch VW, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27(18):3007-3013.

11. Nivolumab (Opdivo) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; April 2021.

12. Scherpereel A, Mazieres J, Greillier L, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial [published correction appears in Lancet Oncol. 2019 Mar;20(3):e132]. Lancet Oncol. 2019;20(2):239-253.

13. Zalcman G, Mazieres J, Greillier L, et al. Second/third-line nivolumab vs nivo plus ipilimumab in malignant pleural mesothelioma: Long-term results of IFCT-1501 MAP52 phase IIR trial with a focus on hyperprogression (HPD) [abstract] Ann Oncol. 2019;30(suppl_5):747-755.

14. Baas P, Scherpereel A, Nowak A, et al. First-line nivolumab + ipilimumab vs chemotherapy in unresectable malignant pleural mesothelioma (CHECKMATE 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386.

15. Ipilimumab (Yervoy) [package insert]. Princeton, NJ: Bristol-Myers Squibb; May 2021.

16. Disselhorst MJ, Quispel-Janssen J, Lalezari F, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019;7(3):260-270.

17. Bevacizumab (Avastin) [package insert]. South San Francisco, CA: Genentech Inc; December 2020.

18. 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 [published correction appears in Lancet. 2016 Apr 2;387(10026):e24]. Lancet. 2016;387(10026):1405-1414.

19. Ceresoli GL, Zucali PA, Mencoboni M, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013;109(3):552-558.

20. Gemcitabine [package insert]. Manalapan, NJ: Armas Pharmaceuticals, Inc; January 2020.

21. Nowak AK, Byrne MJ, Williamson R, et al. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer. 2002;87(5):491-496.

22. van Haarst JM, Baas P, Manegold Ch, et al. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002;86(3):342-345.

23. Taylor P, Castagneto B, Dark G, et al. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008;3(7):764-771.

24. 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. 2008;26(10):1698-1704.

25. Zucali PA, Simonelli M, Michetti G, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012;75(3):360-367.

26. Vinorelbine (Navelbine) [package insert]. Parsippany, NJ: Pierre Fabre Pharmaceuticals Inc; January 2020.

27. Muers MF, Stephens RJ, Fisher P, et al. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet. 2008;371(9625):1685-1694.

28. Stebbing J, Powles T, McPherson K, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009;63(1):94-97.

29. Zauderer MG, Kass SL, Woo K, Sima CS, Ginsberg MS, Krug LM. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014;84(3):271-274.

30. Quispel-Janssen J, van der Noort V, de Vries JF, et al. Programmed death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13(10):1569-1576.

31. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co Inc; May 2021.

32. Metaxas Y, Rivalland G, Mauti LA, et al. Pembrolizumab as palliative immunotherapy in malignant pleural mesothelioma. J Thorac Oncol. 2018;13(11):1784-1791.

33. Alley EW, Lopez J, Santoro A, et al. 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. Lancet Oncol. 2017;18(5):623-630.

34. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation [published correction appears in Eur J Cancer. 2021 Feb;144:400]. Eur J Cancer. 2020;131:68-75.

(Revised 7/2021; NCCN Malignant Peritoneal Mesothelioma Guidelines v2.2021) © 2021 by Haymarket Media, Inc.