The Nurse View: Practice Pearls in the Use of Immune Checkpoint Inhibitors in Advanced NSCLC Moderator Kristen Kreamer, MSN, CRNP, AOCNP Nurse Practitioner Fox Chase Cancer Center Philadelphia, Pennsylvania Title Slide Layout Panelist Beth Eaby-Sandy, MSN, CRNP, OCN Nurse Practitioner Abramson Cancer Center University of Pennsylvania Philadelphia, Pennsylvania

This program will include a discussion of off-label treatment not approved by the FDA for use in the US, and data that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal. Divider Slide Layout

Checkpoint Inhibitors Approved in NSCLC Pembrolizumab[a] First-Line Nivolumab[b] Atezolizumab[c] Second-Line NSCLC = non-small cell lung cancer a. Keytruda® [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2016. b. Opdivo® [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2016. c. Tecentriq® [package insert]. South San Francisco, CA: Genentech Inc; 2016. a. Keytruda® 2016. b. Opdivo ® 2016. c. Tecentriq® 2016.

Immunotherapy vs Chemotherapy Adverse events are different Toxicities are managed differently Immunotherapy Fatigue Nausea Decreased appetite Asthenia Diarrhea Hypothyroidism Rash Chemotherapy Bone marrow suppression Nephrotoxicity Hearing loss Kreamer KM. Immune checkpoint blockade: A new paradigm in treated advanced cancer. J Adv Pract Oncol. 2014;5:418-431. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. 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. 2016;387:1540-1550. Kreamer KM. J Adv Pract Oncol. 2014;5:418-431; Brahmer J, et al. N Engl J Med. 2015;373:123-135; Borghaei H, et al. N Engl J Med. 2015;373:1627-1639; Herbst RS, et al. Lancet. 2016;387:1540-1550. 4

Overview of Immune Regulation Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13:227-242. Kreamer KM. Immune checkpoint blockade: A new paradigm in treated advanced cancer. J Adv Pract Oncol. 2014;5:418-431. Immune system surveys for tumors Downregulation of immune system Immunotherapy prevents downregulation Chen L, Flies DB. Nat Rev Immunol. 2013;13:227-242. Kreamer KM. J Adv Pract Oncol. 2014;5:418-431.

Basics of Immunotherapy Tumor PD-L1 PD-1 Anti-PD-1/ PD-L1 Activated T cell Resting T cell No Inhibition of killing PD-L1 PD-1 LYMPH NODE CD28 Inhibition of killing © Medscape, LLC TCR CD38 = cluster of differentiation 38; PD-1 = programmed death-1; PD-L1 = programmed death-ligand 1; TCR = antigen (t cell) receptor Jiang T, Zhou C. The past, present and future of immunotherapy against tumor. Transl Lung Cancer Res. 2015;4:253-264. Kreamer KM. Immune checkpoint blockade: A new paradigm in treated advanced cancer. J Adv Pract Oncol. 2014;5:418-431. Tumor antigen Dendritic cell MHC B7 Jiang T, Zhou C. Transl Lung Cancer Res. 2015;4:253-264. Kreamer KM. J Adv Pract Oncol. 2014;5:418-431.

CheckMate Trial Design CheckMate 017/057[a,b] Second-line in advanced NSCLC PD-L1 expression not required for enrollment Nivolumab vs docetaxel Primary endpoint: OS CheckMate 026[c] First-line in advanced NSCLC PD-L1 expression of ≥5% required for enrollment Nivolumab vs investigators choice chemotherapy Primary endpoint: PFS NSCLC = non-small cell lung cancer; OS = overall survival; PFS = progression-free survival; SCLC = small cell lung cancer a. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135. b. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. c. Socinski M, Creelan B, Horn L, et al. CheckMate 026: A phase 3 trial of nivolumab vs investigator’s choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage iv/recurrent programmed death ligand 1 (PD-L1)-positive NSCLC [ESMO abstract LBA7). Presented at ESMO 2016 Congress. a. Brahmer J, et al. N Engl J Med. 2015;373:123-135. b. Borghaei H, et al. N Engl J Med. 2015;373:1627-1639. c. Socinski M, et al. ESMO 2016. Abstract LBA7.

Outcomes With Nivolumab mOS, mo mPFS, mo ORR, % AEs of Any Grade, % 2-year Survival, %*[d] CheckMate 017 (squamous, second line)[a] Nivo (n = 131) 9.2 3.5 20 58 23 Doce (n = 129) 6.0 2.8 9 86 8 CheckMate 057 (nonsquamous, second line)[b] Nivo (n = 287) 12.2 2.3 19 69 29 Doce (n = 268) 9.4 4.2 12 88 16 CheckMate 026 (≥5% PD-L1 expression, first line)[c] Nivo (n = 211) 14.4 26.1 71.2 Not reported Chemo (n = 212) 13.2 5.9 33.5 92.4 AE = adverse event; doce = docetaxel; mOS = median overall survival; mPFS = median progression-free survival; ORR = overall response rate; nivo = nivolumab a. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135. b. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. c. Socinski M, Creelan B, Horn L, et al. CheckMate 026: A phase 3 trial of nivolumab vs investigator’s choice (IC) of platinum-based doublet chemotherapy (PT-DC) as first-line therapy for stage iv/recurrent programmed death ligand 1 (PD-L1)-positive NSCLC [ESMO abstract LBA7). Presented at ESMO 2016 Congress. d. Borghaei H, Brahmer J, Horn L, et al. Nivolumab vs docetaxel in patients with advanced NSCLC: CheckMate 017/057 2-year update and exploratory cytokine profile analysis [ASCO abstract 9025]. J Clin Oncol. 2016;34(suppl). *n = 135 for nivo and 137 for doce in CheckMate 017; 292 for nivo and 290 for doce in CheckMate 057. a. Brahmer J, et al. N Engl J Med. 2015;373:123-135; b. Borghaei H, et al. N Engl J Med. 2015;373:1627-1639; c. Socinski M, et al. ESMO abstract LBA7. 2016; d. Borghaei H, et al. J Clin Oncol. 2016;34. [ASCO® 2016, abstract 9025].

KEYNOTE Trial Design KEYNOTE-001[a] KEYNOTE-010[b] First and second-line in advanced NSCLC PD-L1 expression of ≥1% required for enrollment Pembrolizumab 2 mg/kg or 10 mg/kg Primary endpoints: safety, side-effect profile, antitumor activity KEYNOTE-010[b] Second-line in advanced NSCLC PD-L1 expression of ≥1% required for enrollment Pembrolizumab 2 mg/kg, 10 mg/kg, or docetaxel Primary endpoints: OS, PFS NSCLC = non-small cell lung cancer; OS = overall survival; PD-L1 = programmed death-ligand 1; PFS = progression-free survival a. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-2028. b. 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. 2016;387:1540-1550. a. Garon EB, et al. N Engl J Med. 2015;372:2018-2028. b. Herbst RS, et al. Lancet. 2016;387:1540-1550.

Outcomes With Pembrolizumab ORR, % mPFS, mo mOS, mo AEs Any Grade, % 2-Year Survival, %[c] KEYNOTE-001 (≥1% PD-L1 expression)[a] Treatment Naive (n = 101) 24.8 6.0 16.2 44.5 Previously Treated (n = 394) 18 3.0 9.3 31.3* KEYNOTE-010 (≥50% PD-L1 expression, second line)[b] Pembro, 2 mg/kg (n = 344) 30 5.0 14.9 63** Doce (n = 343) 8 4.1 8.2 81 AE = adverse event; mOS = median overall survival; mPFS = median progression-free survival; ORR = overall response rate; PD-L1 = programmed death-ligand 1; pembro = pembrolizumab Sync 03:05 a. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-2028. b. 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. 2016;387:1540-1550. c. Hui R, Gandhi L, Costa EC, et al. Long-term OS for patients with advanced NSCLC enrolled in the KEYNOTE-001 study of pembrolizumab (pembro) [ASCO abstract 9026]. J Clin Oncol. 2016;34(suppl). PD-L1 expression must be confirmed as ≥50% for first-line and ≥1% for second-line before treatment with pembrolizumab *n = 449. **n = 339. a. Garon EB, et al. N Engl J Med. 2015;372:2018-2028; b. Herbst RS, et al. Lancet. 2016;387:1540-1550; c. Hui R, et al. J Clin Oncol. 2016;34(suppl). [ASCO® abstract 9026.]

KEYNOTE-024 Trial Design First-line for advanced NSCLC Pembrolizumab vs platinum-based chemotherapy regimens PD-L1 expression of ≥50% Primary endpoint: PFS NSCLC = non-small cell lung cancer; PD-L1 = programmed death-ligand 1; PFS = progression-free survival Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016. [Epub ahead of print.] Reck M, et al. N Engl J Med. 2016. [Epub ahead of print.]

Outcomes With First-Line Pembrolizumab Chemotherapy n = 151 PFS, mo 10.3 6.0 6-month OS, % 80.2 72.4 mOS, mo NR ORR, % 44.8 27.8 mDOR, mo 6.3 AEs any grade, % 73.4 90.0* AE = adverse event; mDOR = median duration of response; NR = not reached; ORR = overall response rate; OS = overall survival; PFS = progression-free survival *n = 150. Reck M, et al. N Engl J Med. 2016. [Epub ahead of print.]

OAK Trial Design Second-line for NSCLC Atezolizumab vs docetaxel Primary endpoint: OS NSCLC = non-small cell lung cancer; OS = overall survival Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Presented at European Society for Medical Oncology (ESMO) 2016 Congress, Copenhagen, Denmark; October 7-11, 2016. Abstract LBA44. Barlesi F, et al. ESMO 2016. Abstract LBA44.

Outcomes With Atezolizumab n = 425 Docetaxel mOS, mo 13.8 9.6 mPFS, mo 2.8 4.0 ORR, % 14 13 mDOR, mo AEs Any Grade, % 64 86 AE = adverse event; CNS = central nervous system; mDOR = median duration of response; mOS = median overall survival; mPFS = median progression-free survival; ORR = overall response rate; OS = overall survival; PD-L1 = programmed death-ligand 1 Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Presented at European Society for Medical Oncology (ESMO) 2016 Congress, Copenhagen, Denmark; October 7-11, 2016. Abstract LBA44. OS benefit was independent of histology, PD-L1 expression levels, presence of CNS metastases, and smoking status Barlesi F, et al. ESMO 2016. Abstract LBA44.

Most Common TRAEs With Immunotherapy Gastrointestinal Nausea Diarrhea Decreased appetite Endocrine Hypothyroidism Hyperthyroidism Muscular Fatigue Asthenia TRAE= treatment-related adverse event Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123-135. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639. 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. 2016;387:1540-1550. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016. [Epub ahead of print.] Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Presented at European Society for Medical Oncology (ESMO) 2016 Congress, Copenhagen, Denmark, October 7-11, 2016. Abstract LBA44. Skin Rash Dermatitis Brahmer J, et al. N Engl J Med. 2015;373:123-135; Borghaei H, et al. N Engl J Med. 2015;373:1627-1639; Herbst RS, et al. Lancet. 2016;387:1540-1550; Reck M, et al. N Engl J Med. 2016. [Epub ahead of print]; Barlesi F, et al. ESMO 2016. Abstract LBA44.

Management of AEs Rash or dermatitis Usually mild, but can be exacerbated Treat with topical corticosteroids Nausea Treat with 5-HTP antagonist Typically no vomiting or weight loss Fatigue Can be limiting, but is not typically as intense as with chemotherapy Immunotherapy is not recommended in patients with autoimmune disorders or who are post-transplant 5-HTP = 5-hydroxytryptophan; AE = adverse event Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016:e1-e8. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse reactions of anti-PD-L1 antibody therapy. Cancer Treat Rev. 2016;45:7-18. O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Opdivo® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2016. Keytruda® [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2015. Tecentriq® [package insert]. Genentech, Inc: South San Francisco, CA; 2016. Friedman CF, et al. JAMA Oncol. 2016:e1-e8; Eigentler TK, et al. Cancer Treat Rev. 2016;45:7-18; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print]; Opdivo® 2016; Keytruda® 2015; Tecentriq® 2016.

Grading of AEs There is no grading scale for immune-mediated toxicities Toxicities may be included in CTCAE, but management of immune-mediated toxicity is different CTCAE Organized by system organ class Defines grade based on symptoms Provides management guidance Currently on version 4.0 Used in clinical trials more than in daily practice AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events US Department of Health and Human Services. Common terminology criteria for adverse events (CTCAE). Version 4.0. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed October 31, 2016. HHS website.

Management of irAEs Based on Grade Continue therapy Provide supportive care Grade 2 Withhold therapy Start corticosteroids at lower doses Grade 3 Withhold therapy Start or increase dose of corticosteroids Grade 4 Discontinue therapy Start or increase dose of corticosteroids irAE = immune-related adverse event Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016:e1-e8. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse reactions of anti-PD-L1 antibody therapy. Cancer Treat Rev. 2016;45:7-18. O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Taper steroids slowly—over at least 1 month Friedman CF, et al. JAMA Oncol. 2016:e1-e8; Eigentler TK, et al. Cancer Treat Rev. 2016;45:7-18; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Management of Diarrhea/Colitis Manage diarrhea with medications and electrolyte supplements Have patients be alert that this could be a precursor to colitis Colitis Hold therapy and start steroids for grade 2 colitis that persists >5 days or recurs and for grade 3 to 4 Progresses quickly Consider GI consult or lower-GI endoscopy GI = gastrointestinal Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Management of Pneumonitis Presents with shortness of breath and cough Need to differentiate between cancer symptoms, COPD symptoms, infection, and pneumonitis Consider pulmonary and infectious disease consults Consider bronchoscopy for severe presentation Hold therapy and administer steroids for grades 2 to 4 Follow-up Grade 1: reassess every 1 to 3 weeks, resume treatment when stable Grade 2: reassess every 1 to 3 days, taper steroids over 1 month before resuming Slowly taper steroids COPD = chronic obstructive pulmonary disease Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Management of Steroid-Refractory irAEs Consider addition of mycophenolate mofitil or infliximab Typically done in an inpatient setting irAE = immune-related adverse event Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Restarting Immunotherapy Consider on a case-by-base basis taking maximum grade of AE experienced into consideration May be able to restart immunotherapy once patients is tapered off of steroids and AE has resolved to grade 1 or 0 Assess response prior to AE to aid decision to restart AE = adverse events Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Management of Hypothyroidism Monitor with TSH Manage with hormone replacement Consider endocrinology consult Continue immunotherapy Inform patients that hormone replacement will be lifelong TSH = thyroid-stimulating hormone Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

Importance of Patient Education Patients should be aware of differences between checkpoint inhibitors and chemotherapy Patients should also be aware of timing of symptoms Typically peak between 6 to 12 weeks Still a concern even late in course in therapy Patients should know who to call to report an AE Stress the need to call immediately as AEs can be life-threatening and to not be afraid of calling due to change of holding anti-cancer therapy Educational materials such as wallet cards are available for both approved checkpoint inhibitors Use patient consent forms as alternative AE = adverse event Fecher LA. Agarwala SS, Hodi FS, Weber JS. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist. 2013;18:733-743. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2016;2:1346-1353. Eigentler TK, Hassel JC, Berking C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev. 2016. [Epub ahead of print.] O’Kane GM, Labbe C, Doherty MK, Young K, Albaba H, Leighl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2016. [Epub ahead of print]. Fecher LA, et al. Oncologist. 2013;18:733-743; Friedman CF, et al. JAMA Oncol. 2016;2:1346-1353; Eigentler TK, et al. Cancer Treat Rev. 2016. [Epub ahead of print]; O’Kane GM, et al. Oncologist. 2016. [Epub ahead of print].

The Future of Immunotherapy There is ongoing research examining antibodies targeting other checkpoint molecules both in the first and second line setting as well as combination therapies Continue to monitor AEs closely with new approvals New interventions may be developed for managing AEs AE = adverse event

Key Takeaways Checkpoint inhibitors are a new option for lung cancer treatment While superior to chemotherapy in some situations, checkpoint inhibitors are not a replacement for chemotherapy AEs are different with checkpoint inhibitors—be on the watch for them, involve patients, and treat appropriately AE = adverse events

Abbreviations 5-HTP = 5-hydroxytryptophan AE = adverse event CD38 = cluster of differentiation 38 CNS = central nervous system COPD = chronic obstructive pulmonary disease CTCAE = Common Terminology Criteria for Adverse Events doce = docetaxel GI = gastrointestinal irAE = immune-related adverse event mDOR = median duration of response mOS = median overall survival mPFS = median progression-free survival nivo = nivolumab NSCLC = non-small cell lung cancer ORR = overall response rate OS = overall survival PD-1 = programmed death-1 AE = adverse events

Abbreviations (cont) PD-L1 = programmed death-ligand 1 pembro = pembrolizumab PFS = progression-free survival SCLC = small cell lung cancer TCR= antigen (t cell) receptor TRAE= treatment-related adverse event TSH = thyroid-stimulating hormone AE = adverse events