Download presentation
Presentation is loading. Please wait.
1
Expert Perspectives on Immunotherapy for NSCLC: Practical Guidance and Recommendations
NSCLC, non-small-cell lung cancer. This program is supported by an educational grant from Merck and Co., Inc.
2
About These Slides Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients When using our slides, please retain the source attribution: These slides may not be published, posted online, or used in commercial presentations without permission. Please contact for details Slide credit: clinicaloptions.com Disclaimer: The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
3
Co-Chairs Leora Horn, MD, MSc, FRCPC Associate Professor of Medicine Clinical Director, Thoracic Oncology Research Program Assistant Vice Chairman for Faculty Development Vanderbilt Ingram Cancer Center Nashville, Tennessee Melissa L. Johnson, MD Associate Director, Lung Cancer Research Sarah Cannon Research Institute Nashville, Tennessee This slide lists the faculty who were involved in the production of these slides.
4
Faculty Disclosures Leora Horn, MD, MSc, FRCPC, has disclosed that she has received consulting fees from AbbVie, Bayer, Bristol-Myers Squibb, Genentech, Lilly, and Merck and fees for non-CME/CE services from Xcovery. Melissa L. Johnson, MD, has disclosed that she has received consulting fees from AbbVie, Celgene, and Genentech and funds for research support from Array, AstraZeneca, BerGenBio, Checkpoint Therapeutics, EMD Serono, Genmab, Genentech/Roche, Janssen, Kadmon, Lilly, Mirati Therapeutics, Novartis, OncoMed, Pfizer, Regeneron, and Stemcentrx.
5
Outline Overview of the Treatment of Advanced NSCLC
Clinical Application of Immunotherapy for Advanced NSCLC Newly Diagnosed Disease Progressive Disease Management of Treatment-Related Adverse Events Emerging Therapeutic Strategies With Immune Checkpoint Inhibitors NSCLC, non-small-cell lung cancer.
6
Overview
7
Lung Cancer Remains a Major Global Health Burden
One of the most common cancers and leading cause of cancer deaths in US and worldwide[1,2] New cases, 2017 (estimated): US, 222,500; global, 1.8 million Deaths, 2017 (estimated): US, 155,870; global, 1.6 million ~ 80% to 85% of cases are NSCLC (~ 184,000)[3] Stage IV at diagnosis: ~ 57%[4] Represented by multiple disease subtypes[5] Standard of care for stage IV NSCLC: systemic therapy NSCLC, non-small-cell lung cancer. 1. GLOBOCAN Cancer Fact Sheets Siegel RL, et al. CA Cancer J Clin. 2016;66: American Cancer Society. Non-small-cell Lung Cancer. 4. SEER Cancer Statistics Review, Li T, et al. J Clin Oncol. 2013;31: Slide credit: clinicaloptions.com
8
Checkpoint Inhibitors subtyping for chemotherapy Genomics-driven TKIs:
What Tools Can Facilitate Personalized Therapy in Advanced-Stage NSCLC? Chemotherapy Targeted Therapy Checkpoint Inhibitors Histologic subtyping for chemotherapy Genomics-driven TKIs: EGFR ALK ROS1 Anti–PD-1 Anti–PD-L1 Anti–CTLA-4 NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor. How do we optimize therapy in individual pts (ie, first line, second line, third line)? Slide credit: clinicaloptions.com
9
CTLA-4 and PD-1/PD-L1 Checkpoint Blockade for Cancer Treatment
Priming phase (lymph node) Effector phase (peripheral tissue) T-cell migration Dendritic cell Cancer cell T-cell T-cell Dendritic cell T-cell MHC TCR B7 CD28 CTLA-4 TCR MHC PD-1 mAbs: Nivolumab Pembrolizumab PD-L1 mAbs: Atezolizumab Avelumab Durvalumab CTLA-4 mAbs: Ipilimumab Tremelimumab T-cell PD-1 Cancer cell PD-L1 Slide credit: clinicaloptions.com Ribas A. N Engl J Med. 2012;366:
10
Clinical Application of Immunotherapy for Advanced NSCLC
11
Therapeutic Plateau in Metastatic NSCLC ECOG 1594
1.0 Cisplatin/paclitaxel Cisplatin/gemcitabine Cisplatin/docetaxel Carboplatin/paclitaxel 0.8 0.6 OS (%) 0.4 ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer. 0.2 5 10 15 20 25 30 Mos Slide credit: clinicaloptions.com Schiller JH, et al. N Engl J Med. 2002;346:92-98.
12
KEYNOTE-024: Pembrolizumab vs CT as First-line Therapy for Advanced NSCLC
Open-label phase III trial Primary endpoint: PFS Secondary and exploratory endpoints: ORR, OS, DoR, and safety Pts with stage IV NSCLC and ECOG PS 0/1, no previous systemic therapy, no actionable EGFR/ALK mutations, and PD-L1 TPS ≥ 50%* (N = 305) Pembrolizumab 200 mg IV Q3W for up to 35 cycles (n = 154) Chemotherapy (histology based) for up to 6 cycles (n = 151) Stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and enrollment region Until PD (crossover to pembrolizumab allowed) *≥ 50% tumor cell staining using 22C3 companion diagnostic IHC assay. Until PD or unacceptable toxicity CT, chemotherapy; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; PD, progressive disease; PS, performance status; TPS, tumor proportion score. Slide credit: clinicaloptions.com Reck M, et al. N Engl J Med. 2016;375:
13
KEYNOTE-024: Survival Outcomes
PFS OS Pembro (n = 154) CT (n = 151) Median PFS, mos 10.3 6.0 HR (95% CI) 0.50 ( ); P < .001 Pembro (n = 154) CT (n = 151) Median OS, mos NR HR (95% CI) 0.60 ( ); P = .005 100 100 80 80 60 60 PFS (%) OS (%) 40 40 CT, chemotherapy; NR, not reached; Pembro, pembrolizumab. 20 20 3 6 9 12 15 18 3 6 9 12 15 18 21 Mos Mos Slide credit: clinicaloptions.com Reck M, et al. N Engl J Med. 2016;375:
14
CheckMate-026: Nivolumab vs CT in First-line Therapy for Advanced NSCLC
Randomized, open-label phase III trial Primary endpoint: PFS (≥ 5% PD-L1 positive) Secondary endpoints: PFS (≥ 1% PD-L1 positive), ORR, OS Pts with stage IV/recurrent NSCLC, no previous systemic therapy, no actionable EGFR/ALK mutations, PD-L1 expression ≥ 1%* (N = 541) Nivolumab 3 mg/kg IV Q2W (n = 271) Chemotherapy (histology based) for up to 6 cycles (n = 270) Until PD or unacceptable toxicity Stratified by PD-L1 expression (< 5% vs ≥ 5%) and histology (squamous vs nonsquamous) Until PD (crossover to nivolumab allowed) CT, chemotherapy; NSCLC, non-small-cell lung cancer; PD, progressive disease. *≥ 1% tumor cell staining using 28-8 complementary diagnostic IHC assay. Slide credit: clinicaloptions.com Socinski M, et al. ESMO Abstract LBA7_PR.
15
CheckMate-026: Survival Outcomes in Pts With ≥ 5% PD-L1 Expression
Nivo (n = 211) CT (n = 212) Median PFS, mos 4.2 5.9 HR (95% CI) 1.15 ( ); P =.2511 Nivo (n = 211) CT (n = 212) Median OS, mos 14.4 13.2 HR (95% CI) 1.02 ( ) 100 100 80 80 60 60 PFS (%) OS (%) Chemotherapy 40 40 Nivolumab 20 20 CT, chemotherapy; Nivo, nivolumab. Nivolumab Chemotherapy 3 6 9 12 15 18 21 24 27 3 6 9 12 15 18 21 24 27 Mos Mos Slide credit: clinicaloptions.com Socinski M, et al. ESMO Abstract LBA7_PR.
16
Blueprint PD-L1 IHC Assay Comparison Project: Phase 1
Analytical comparison of % tumor cell staining (tumor proportion score), by case (n = 39), for each assay Data points represent the mean score from 3 pathologists for each assay on each case Superimposed lines/points indicate identical TPS values No clinical diagnostic cutoff applied Conclusion: 3 of 4 assays are analytically similar for tumor cell staining 22C3 (pembrolizumab), 28-8 (nivolumab), and SP263 (avelumab) 100 22C3 28-8 SP142 SP263 80 60 % Tumor Cell Staining 40 20 TPS, tumor proportion score. 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 Cases SP142 (atezolizumab) Slide credit: clinicaloptions.com Hirsch FR et al. J Thorac Oncol. 2017;12:
17
Evaluable Samples for PD-L1 Testing
PD-L1 Testing in FNA and Cytology Samples in the Community Practice Setting Evaluable Samples for PD-L1 Testing Evaluable Samples (%) 20 40 60 80 100 90% 82% 79% 75% 90 104 127 50 63 9 12 Evaluable samples, n Samples analyzed, n Excisional Core Needle FNA Other Cytology FNA, fine needle aspiration; NSCLC, non-small-cell lung cancer. 302 NSCLC specimens were analyzed retrospectively for PD-L1 expression using the 28‑8 antibody per the diagnostic label Slide credit: clinicaloptions.com Hussein M et al., CMSTO Abstract ORAL01.02
18
CheckMate 017 and 057: Nivolumab vs Docetaxel in Previously Treated Advanced NSCLC
Open-label, randomized phase III trials Primary endpoint: OS Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL CheckMate 017: Squamous NSCLC CheckMate 057: Nonsquamous NSCLC Pts with stage IIIB/IV squamous NSCLC and ECOG PS 0-1 with failure of 1 previous platinum doublet chemotherapy (N = 272) Nivolumab 3 mg/kg IV Q2W (n = 135) Nivolumab 3 mg/kg IV Q2W (n = 292) Pts with stage IIIB/IV nonsquamous NSCLC and ECOG PS 0-1 who failed 1 prior platinum doublet chemotherapy ± TKI therapy (N = 582) Until disease progression or unacceptable toxicity Until disease progression or unacceptable toxicity Docetaxel 75 mg/m2 IV Q3W (n = 137) Docetaxel 75 mg/m2 IV Q3W (n = 290) ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; PS, performance status; QoL, quality of life; TKI, tyrosine kinase inhibitor. Speaker notes: 017 stratification factors – previous paclitaxel therapy (yes or no) and region 057 stratification factors – previous maintenance therapy ( yes or no) and line of therapy (2nd vs 3rd line) Brahmer J, et al. N Engl J Med. 2015;373: Borghaei H, et al. N Engl J Med. 2015;373: Slide credit: clinicaloptions.com
19
CheckMate 017 and 057: OS With a Minimum 2-Yr Follow-up
CheckMate 017: Squamous CheckMate 057: Nonsquamous 100 100 Nivo (n = 135) Docetaxel (n = 137) Median OS, mos 9.2 6.0 1-yr OS, % 42 24 2-yr OS, % 23 8 HR (95% CI) 0.62 ( ) Nivo (n = 292) Docetaxel (n = 290) Median OS, mos 12.2 9.5 1-yr OS, % 51 39 2-yr OS, % 29 16 HR (95% CI) 0.75 ( ) 80 80 60 60 OS (%) OS (%) 40 40 Nivolumab 20 Nivolumab 20 Nivo, nivolumab. Docetaxel Docetaxel 3 6 9 12 15 18 21 24 27 30 33 36 39 3 6 9 12 15 18 21 24 27 30 33 36 39 Mos Mos Pts at Risk, n Nivolumab Docetaxel Pts at Risk, n Nivolumab Docetaxel 135 137 113 104 86 69 69 46 57 33 51 22 38 17 34 14 29 11 19 9 14 6 7 4 1 292 290 233 243 194 171 150 148 111 128 89 112 66 97 53 81 45 46 25 18 6 6 3 1 Slide credit: clinicaloptions.com Borghaei H, et al. ASCO Abstract 9025.
20
CheckMate 017: OS by PD-L1 Expression in Squamous NSCLC
1% PD-L1 Expression Level 5% PD-L1 Expression Level 10% PD-L1 Expression Level Median OS, Mos Nivo Doc PD-L1 ≥ 1% 9.3 7.2 PD-L1 < 1% 8.7 5.9 Median OS, Mos Nivo Doc PD-L1 ≥ 5% 10 6.4 PD-L1 < 5% 8.5 6.1 Median OS, Mos Nivo Doc PD-L1 ≥ 10% 11 7.1 PD-L1 < 10% 8.2 6.1 100 100 100 80 80 80 60 60 60 OS (%) 40 40 40 20 20 20 Doc, docetaxel; Nivo, nivolumab; NSCLC, non-small-cell lung cancer. 3 6 9 12 15 18 21 24 3 6 9 12 15 18 21 24 3 6 9 12 15 18 21 24 Mos Mos Mos Nivolumab PD-L1+ Nivolumab PD-L1- Docetaxel PD-L1+ Docetaxel PD-L1- Slide credit: clinicaloptions.com Brahmer J, et al. N Engl J Med. 2015;373:
21
CheckMate 057: 2-Yr OS Rates
CheckMate 057: 2-Yr OS Rates* by PD-L1 Expression Level in Nonsquamous NSCLC PD-L1 expression level associated with magnitude of 2-yr OS benefit starting at lowest level examined (1%) 100 Nivolumab Docetaxel Overall PD-L1 Expression 80 60 OS (%) 40 20 44 45 37 29 25 NSCLC, non-small-cell lung cancer. 16 18 17 14 13 n = 292 290 108 191 123 123 95 86 86 79 All Pts < 1% ≥ 1% ≥ 5% ≥ 10% HR† (95% CI) ( ) ( ) ( ) ( ) ( ) *Rates are Kaplan-Meier estimates, error bars indicate 95% CI. †Comparison of full Kaplan-Meier survival curves for each tx group. Slide credit: clinicaloptions.com Borghaei H, et al. ASCO Abstract 9025.
22
KEYNOTE-010: Pembrolizumab vs Docetaxel in Advanced PD-L1–Positive NSCLC
Multicenter, randomized, open-label phase II/III trial Primary endpoints: OS, PFS Secondary endpoints: DoR, ORR, safety Pembrolizumab 2 mg/kg IV Q3W (n = 345) Docetaxel 75 mg/m2 IV Q3W (n = 343) Treatment continued for 24 mos or until PD or unacceptable toxicity Pts with advanced NSCLC who progressed after platinum-based chemotherapy (and TKI if EGFR+ or ALK+); ≥ 1% PD-L1+ tumor cells; ECOG PS 0/1 (N = 1034) Pembrolizumab 10 mg/kg IV Q3W (n = 346) DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; PD, progressive disease; PS, performance status; TKI, tyrosine kinase inhibitor. Speaker notes: Stratification factors - Stratified by ECOG PS (0 vs 1), region (east Asia vs not east Asia), and PD-L1 expression (≥ 50% vs 1% to 49%) Corticosteroid premedication allowed with docetaxel Disease progression determined by radiological imaging. In the case of investigator-assessed clinical disease progression, treatment permitted until confirmatory scan completed 4-6 wks later. Slide credit: clinicaloptions.com Herbst RS, et al. Lancet. 2016;387:
23
KEYNOTE-010: OS in Pts With PD-L1 TPS ≥ 1% and TPS ≥ 50%
mOS, Mos 1-Yr OS, % HR (95% CI) Pembrolizumab 2 mg/kg (n = 344) 10.4 43.2 0.71 ( ) Pembrolizumab 10 mg/kg (n = 346) 12.7 52.3 0.50 ( ) Docetaxel (n = 343) 8.5 34.6 mOS, Mos HR (95% CI) Pembrolizumab 2 mg/kg (n = 139) 14.9 0.54 ( ) Pembrolizumab 10 mg/kg (n = 151) 17.3 0.50 ( ) Docetaxel (n = 152) 8.2 100 100 80 80 60 60 OS (%) OS (%) 40 mOS, median OS; TPS, tumor proportion score 40 20 20 5 10 15 20 25 5 10 15 20 25 Mos Mos Slide credit: clinicaloptions.com Herbst RS, et al. Lancet. 2016;387:
24
KEYNOTE-010: OS in Pts With PD-L1 TPS 1% to 49%
Median OS, Mos (95% CI) 9-Mo OS, % HR (95% CI) Pembrolizumab 2 mg/kg 9.4 ( ) 53 0.79 ( ) Pembrolizumab 10 mg/kg 10.8 ( ) 58 0.71 ( ) Docetaxel 8.6 ( ) 47 – 100 80 60 OS (%) 40 20 TPS, tumor proportion score. 5 10 15 20 25 Pts at Risk, n Mos Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 205 195 191 149 140 122 64 41 29 31 14 9 5 Slide credit: clinicaloptions.com Garon EB, et al. ASCO Abstract 9024.
25
OAK: Atezolizumab vs Docetaxel in Progressive Advanced NSCLC
Multicenter, randomized, open-label phase III trial Primary endpoints (first 850 pts enrolled): OS in ITT population; OS in pts with ≥ 1% PD-L1 expression Secondary endpoints: ORR, PFS, DoR, safety Atezolizumab 1200 mg IV Q3W (n = 425) Docetaxel 75 mg/m2 IV Q3W (n = 425) Metastatic or locally advanced NSCLC (2L/3L), PD on prior platinum-based treatment (N = 1225) Stratified by PD-L1 expression, histology, prior chemotherapy regimens No crossover allowed Until loss of clinical benefit Until PD DoR, duration of response; ITT, intent to treat; NSCLC, non-small-cell lung cancer; PD, progressive disease. Slide credit: clinicaloptions.com Rittmeyer A, et al. Lancet. 2016;389:
26
OAK: OS in ITT Population
100 Landmark OS, % 12 Mos 18 Mos Atezolizumab 55 40 Docetaxel 41 27 80 60 OS (%) HR: 0.73 (95% CI ; P = .0003) 40 20 Median: 9.6 mos (95% CI: ) Median: 13.8 mos (95% CI: ) 3 6 9 12 15 18 21 24 27 Mos Slide credit: clinicaloptions.com Rittmeyer A, et al. Lancet. 2017;389:
27
OAK: OS by PD-L1 Expression
On-Study Prevalence Median OS, Mos Subgroup TC3 or IC3 TC2/3 or IC2/3 TC1/2/3 or IC1/2/3* TC0 and IC0 Atezolizumab 20.5 16.3 15.7 12.6 13.8 Docetaxel 8.9 10.8 10.3 9.6 0.41 16% 0.67 31% 0.74 55% 0.75 45% 0% 20% 40% 60% 80% 100% 0.73 100% ITT* IC, tumor-infiltrating immune cells; ITT, intent to treat; TC, tumor cells. 0.2 1 2 HR* In favor of atezolizumab In favor of docetaxel *Stratified HR for ITT and TC1/2/3 or IC1/2/3 subgroup. Unstratified HR for other subgroups. Slide credit: clinicaloptions.com Rittmeyer A, et al. Lancet. 2017;389:
28
Online Interactive Treatment Decision Support Tool for Advanced NSCLC
5 lung cancer experts: Drs. Gandara, Edelman, Ramalingam, Wakelee, and West Enter specific pt and disease characteristics using drop-down menus NSCLC, non-small-cell lung cancer. Available at: clinicaloptions.com/LungTool
29
Management of ICI Treatment-Related Adverse Events
ICI, immune checkpoint inhibitor
30
Immune-Related AEs With Immunotherapy
Endocrine Hypo- or hyperthyroidism Adrenal insufficiency Hypophysitis Eye Uveitis Iritis Skin Dermatitis exfoliative Vitiligo Alopecia Hepatic Hepatitis, autoimmune Pulmonary Pneumonitis (< 5% incidence) Cardiac Myocarditis Gastrointestinal Colitis Renal Nephritis AE, adverse event. Neurologic Neuropathy Guillain-Barre Myasthenia gravis–like syndrome If not vigilant, may result in more serious immune-related AEs Slide credit: clinicaloptions.com
31
Pts With First Event in Category (n)
Time to Onset of First Treatment-Related Select AE With Nivolumab (Any Grade) Majority of treatment-related AEs occurred within first 3 mos of treatment 10 Skin 9 Gastrointestinal Pulmonary 8 Endocrine 7 Renal Pts With First Event in Category (n) 6 Hypersensitivity/infusion reaction 5 Hepatic 4 3 2 1 AE, adverse event 0-3 > 3-6 > 6-12 > 12-24 Mos Pts still on study, n Pts still on treatment, n Total pts with first event, n Slide credit: clinicaloptions.com Reckamp K, et al. WCLC ORAL02.01.
32
Online Interactive Algorithm Tool for Immune-Related AE Management
Developed by Jeffrey S. Weber, MD, PhD Enter specific organ system affected and severity using drop-down menus AE, adverse event. Available at: clinicaloptions.com/irAETool
33
Immune-Mediated Pneumonitis
Fairly uncommon, but potentially serious Pts at increased risk for pneumonitis NSCLC in the setting of chronic lung inflammation Prior radiation to lung History of COPD Signs and symptoms Shortness of breath Dry cough Decreasing O2 saturation on room air New/increasing oxygen requirements Asymptomatic may be detected just on imaging COPD, chronic obstructive pulmonary disease; NSCLC, non-small-cell lung cancer. Slide credit: clinicaloptions.com
34
Immune-Mediated Dermatitis
Reported in up to 40% of pts with anti–CTLA-4 and anti–PD-1 agents Occasionally severe rashes Onset variable within a few wks of starting to several wks/mos into therapy Rule out other etiologies Generally not infusion related Manage mild/moderate dermatitis with supportive care ± withholding drug Hodi FS, et al. N Engl J Med. 2010;363: Images courtesy L. Horn, Vanderbilt University. Slide credit: clinicaloptions.com
35
Management of Grade 1 Gastrointestinal Treatment-Related Adverse Event
36
Case 4: Management of Grade 3 Gastrointestinal Treatment-Related Adverse Event
A few days later, the pt’s wife calls saying that as of that day he is having approximately episodes of diarrhea/day and is complaining about some abdominal pain
37
General Principles of Immune-Related Toxicity Management
Management generally based on severity of symptoms Grade 1: supportive care ± withhold drug Grade 2: withhold drug, consider redose if toxicity resolves to grade ≤ 1; low-dose corticosteroids (prednisone 1-2 mg/kg/day or equivalent) Grade 3/4: discontinue drug; high-dose corticosteroids (prednisone mg/kg/day or equivalent) tapered over ≥ 1 mo once toxicity resolves to grade ≤ 1 Atezolizumab adverse reaction management brochure. Nivolumab adverse reaction management guide. Pembrolizumab adverse reaction management guide. Slide credit: clinicaloptions.com
38
Future Directions
39
KEYNOTE-021: Pembrolizumab + CT as First-line Therapy for Advanced Nonsquamous NSCLC
Randomized phase II cohort of open-label multicohort trial Primary endpoint: ORR (RECIST v1.1) Secondary endpoints included: PFS, DoR, OS, and safety Pts with stage IIIB/IV nonsquamous NSCLC and ECOG PS 0/1, no previous systemic therapy, no actionable EGFR/ALK mutations (N = 123) Pembrolizumab 200 mg IV + Cb/Pem* Q3W x 4 (n = 60) Cb/Pem* Q3W x 4 (n = 63) Stratified by PD-L1 TPS (< 1% vs ≥ 1%) Pembrolizumab up to 24 mos + Pemetrexed maintenance (optional) Pemetrexed maintenance *Cb AUC 5 mg/mL/min; pem 500 mg/m2. AUC, area under the concentration curve; Cb, carboplatin; CT, chemotherapy; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; Pem, pembrolizumab; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; TPS, tumor proportion score. Slide credit: clinicaloptions.com Langer CJ, et al. Lancet Oncol. 2016;17:
40
KEYNOTE-021: First-line CT ± Pembrolizumab in Advanced NSCLC
CT With Pembrolizumab (n = 56) CT Only (n = 55) 100 100 80 80 ORR: 55% 98% of pts with decrease in tumor burden ORR: 29% 82% of pts with decrease in tumor burden 60 60 40 40 20 20 Best Change From Baseline Tumor Size (%) Best Change From Baseline Tumor Size (%) -20 -20 CT, chemotherapy; NSCLC, non-small-cell lung cancer. -40 -40 -60 -60 -80 -80 -100 -100 Slide credit: clinicaloptions.com Langer CJ, et al. Lancet Oncol. 2016;17:
41
KEYNOTE-021: First-line CT + Pembrolizumab vs CT Only
PFS OS Pembro + CT CT Alone Median PFS, mos 13.0 8.9 HR (95% CI) 0.53 ( ) P value .01 100 100 80 80 60 60 Pembro + CT CT Alone Estimated 6-mo survival, % 92 HR (95% CI) 0.90 ( ) P value .39 PFS (%) 40 OS (%) 40 20 20 CT, chemotherapy; Pembro, pembrolizumab. 5 10 15 20 5 10 15 20 Mos Pts at Risk, n (number censored) Pembro + CT CT Pts at Risk, n (number censored) Pembro + CT CT Mos 60 (0) 63 (0) 43 (5) 32 (10) 20 (20) 13 (21) 1 (36) 1 (29) 0 (37) 3 (30) 60 (0) 63 (0) 53 (3) 57 (1) 33 (18) 31 (20) 5 (42) 6 (43) 0 (47) 0 (49) Slide credit: clinicaloptions.com Langer CJ, et al. Lancet Oncol. 2016;17:
42
KEYNOTE-021: Treatment-Related Adverse Events With Incidence ≥15%
Increased AST Increased ALT Decreased Neutrophils 1/2 Grade 3/4 Pembro + CT CT alone Fatigue Nausea Anemia Rash Vomiting Diarrhea Constipation Decreased Appetite Dysgeusia 32 54 20 11 19 10 64 40 58 44 17 12 13 27 15 18 ALT, alanine aminotransferase; CT, chemotherapy; Pembro, pembrolizumab. Slide credit: clinicaloptions.com Langer CJ, et al. Lancet Oncol. 2016;17:
43
Dual Checkpoint Blockade in Advanced NSCLC: Phase I Experience
Trial Pt Population Treatment Key Toxicity Outcomes Key Efficacy Outcomes Study 006 (NCT ) Immunotherapy naive (n = 102) Durvalumab + tremelimumab Multiple dosing cohorts for up to 1 yr Grade 3/4*: 30% Most common (any grade): GI and skin ORR*: 23% Similar ORR for PD-L1 pos or neg CheckMate 012 (NCT ) First line (n = 78) Nivolumab + ipilimumab Multiple dosing cohorts Grade 3/4†: 33% Grade 3/4‡: 37% ORR†: 38% ORR‡: 47% ↑ ORR with ↑ PD-L1 GI, gastrointestinal; neg, negative; NSCLC, non-small-cell lung cancer; pos, positive. *Duravlumab mg/kg Q2W or Q4W + tremelimumab 1 mg/kg Q4W x 6, then Q12W x 3. †Nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg Q6W. ‡Nivolumab 3 mg/kg q2w + ipilimumab 1 mg/kg Q12W. Slide credit: clinicaloptions.com Hellmann MD, et al. Lancet Oncol. 2017;18: Antonia S, et al. Lancet Oncol. 2016;17:
44
Select Ongoing Randomized Phase III Trials of PD-1/PD-L1 Therapy in Advanced NSCLC
Disease Setting Treatment CheckMate 227 (NCT ) First line Nivolumab or nivolumab + ipilimumab or nivolumab + Plt doublet CT vs Plt doublet CT KEYNOTE-042 (NCT ) First line/PD-L1+ Pembrolizumab vs Plt doublet CT KEYNOTE-189 (NCT ) First line (nonsq) Plt/pemetrexed ± pembrolizumab KEYNOTE-407 (NCT ) First line (sq) Cb/pac or nab-pac ± pembrolizumab IMpower 110 (NCT ) Atezolizumab vs Plt doublet CT IMpower 130 (NCT ) Cb/nab-pac vs Cb/nab-pac ± atezolizumab IMpower 131 (NCT ) Cb/pac or nab-pac + atezolizumab vs Cb/nab-pac IMpower 132 (NCT ) Plt/pemetrexed ± atezolizumab IMpower 150 (NCT ) Atezolizumab + Cb/pac ± bev vs Cb/pac/bev JAVELIN Lung 100 (NCT ) Avelumab vs Plt doublet CT JAVELIN Lung 200 (NCT ) Post-CT/PD-L1+ Avelumab vs docetaxel NEPTUNE (NCT ) Durvalumab + tremelimumab vs Plt doublet CT Cb, carboplatin; CT, chemotherapy; nonsq, nonsquamous; NSCLC, non-small-cell lung cancer; pac, paclitaxel; Plt, platinum; sq, squamous Slide credit: clinicaloptions.com *All trials enrolling pts as of February 2017.
45
Conclusions PD-1/PD-L1 inhibitors have expanded treatment options for pts with advanced NSCLC with a potential for durable benefit First-line, high PD-L1 expression (≥ 50%): pembrolizumab Progressive disease: atezolizumab, nivolumab, or pembrolizumab (≥ 1% PD-L1) PD-L1 expression in the tumor is associated with an increased likelihood of response but the predictive validity of this biomarker is still debated Vigilance for immune-related AEs by the entire healthcare team along with rapid intervention is key to optimal management Phase III clinical trials evaluating new combination strategies including checkpoint blockade plus chemotherapy and dual checkpoint blockade are enrolling pts AE, adverse event; NSCLC, non-small-cell lung cancer.
46
Go Online for More CCO Coverage of NSCLC!
Downloadable slidesets on NSCLC CME-certified expert analyses on NSCLC and immunotherapy with expert faculty commentary on all the key studies Interactive Treatment Decision Support Tool for NSCLC— see treatment choices of 5 experts for your patient scenarios clinicaloptions.com/oncology
Similar presentations
© 2025 SlidePlayer.com Inc.
All rights reserved.