NSCLC 2L

KEYTRUDA^®as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumors express PD-L1 with a ≥ 1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumor mutations should also have received targeted therapy before receiving KEYTRUDA^®.

2L = Second Line; ALK = Anaplastic Lymphoma Kinase; EGFR = Epidermal Growth Factor Receptor; NSCLC = Non-Small Cell Lung Cancer; PD-L1 = Programmed Death-Ligand 1; TPS = Tumor Proportion Score

KEYNOTE-010 is an international, randomized, open-label Phase 2/3 trial

The results of this trial were first published with a median follow-up of 31.0 and 42.6 months.
The latest follow-up was published with a median follow-up of 67.4 months.

Patients who discontinued pembrolizumab after achieving complete response, or after 35 cycles/2 years of pembrolizumab, but who experienced disease progression per irRC (determined by investigator) were eligible for up to 17 cycles (1 y) of pembrolizumab retreatment (i.e., second course) if they had received no other anticancer therapy since the last dose of pembrolizumab.

Treatment was continued until disease progression, unacceptable toxicity or for up to 24 months or 35 cycles.

^aPrior therapy must have included ≥2 cycles of platinum-doublet chemotherapy; an appropriate tyrosine kinase inhibitor was required for patients with EGFR/ALK alterations. ^bBecause no differences in OS were observed between the 2 mg/kg and 10 mg/kg pembrolizumab-dose groups in the primary analysis,¹ pembrolizumab doses were pooled for subsequent analyses. ^cPatients randomized to pembrolizumab who completed 35 cycles (~2 years) of pembrolizumab or who stopped pembrolizumab after achieving CR and receiving ≥6 months of treatment, but then had PD, were eligible for second-course pembrolizumab if they had received no other anticancer therapy since the last dose of pembrolizumab. ^dAfter the primary analysis, crossover from docetaxel to pembrolizumab was allowed for patients with PD. ^ePer RECIST v1.1 by independent central review.

ALK = Anaplastic Lymphoma Kinase; CNS = Central Nervous System; CR = Complete Response; DOR = Duration of Response; ECOG PS = Eastern Cooperative Oncology Group Performance Status; EGFR = Epidermal Growth Factor Receptor; ILD = Interstitial Lung Disease; irRC = Immune-Related Response Criteria; IV = intravenous; NSCLC = Non-Small Cell Lung Cancer; n = number; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PD-L1 = Programmed Death-Ligand 1; PFS = Progression-Free Survival; Q3W = 3-weekly dosing; R = Randomized; RECIST = Response Evaluation Criteria in Solid Tumors; TPS = Tumor Proportion Score; y = year.

^aBecause no differences in OS were observed between the 2 mg/kg and 10 mg/kg pembrolizumab-dose groups in the primary analysis, pembrolizumab doses were pooled for this analysis. Data cutoff: April 8, 2020.

ALK = Anaplastic Lymphoma Kinase; ECOG PS = Eastern Cooperative Oncology Group Performance Status; EGFR = Epidermal Growth Factor Receptor; n = number; OS = Overall Survival; PD-L1 TPS = Programmed Death-Ligand 1 Tumor Proportion Score; y = year

At a median follow-up of 67.4 months, KEYTRUDA^® continued to improve OS than docetaxel in previously treated advanced NSCLC patients with PD-L1 ≥50%

Kaplan-Meier estimate of OS (PD-L1 ≥50%):

CI = Confidence Interval; HR = Hazard Ratio; NSCLC = Non-Small Cell Lung Cancer; n = number; no. = number; OS = Overall Survival; PD-L1 = Programmed Death-Ligand 1

At a median follow-up of 67.4 months, KEYTRUDA^® continued to improve OS than docetaxel in previously treated advanced NSCLC patients with PD-L1 ≥1%

Kaplan-Meier estimate of OS (PD-L1 ≥1%):

CI = Confidence Interval; HR = Hazard Ratio; NSCLC = Non-Small Cell Lung Cancer; n = number; no. = number; OS = Overall Survival; PD-L1 = Programmed Death-Ligand 1

5-Year Analysis of ORR and DOR^a by PD-L1 Status:

Median follow-up = 67.4 months (range: 60.0–77.9). Data cutoff: April 8, 2020.
^aPer RECIST v1.1. by independent central review. ^bA “+” symbol indicates there is no progressive disease by the time of last disease assessment. ^cIncludes all patients with a response who are alive, who are progression free, have not initiated new anticancer therapy, and have not been lost to follow-up.

CI = Confidence Interval; DOR = Duration of Response; mDOR = Median Duration of Response; n = number; ORR = Objective Response Rate; PD-L1 = Programmed Death-Ligand 1; RECIST = Response Evaluation Criteria in Solid Tumors; TTR = Time to Response

No new safety signals were identified for KEYTRUDA^® with long-term follow-up

Incidence of Treatment-Related AEs Among Treated Patients:

Median follow-up = 67.4 months (range: 60.0–77.9). Data cutoff: April 8, 2020. ^aDuring treatment with the initially assigned therapy. ^bFor patients who completed the 35 cycles (2 years) of KEYTRUDA^®, grade 3-4 adverse events are reported .

AEs = Adverse Events; n = number; NR = Not Reported; TRAEs = Treatment Related Adverse Events

The recommended dose of KEYTRUDA^® as monotherapy is either 200 mg every 3 weeks (Q3W) or 400 mg every 6 weeks (Q6W) administered as an intravenous infusion over 30 minutes

KEYTRUDA^®: pembrolizumab, 200 mg (Q3W) or 400 mg (Q6W)

Q3W = 3-weekly dosing; Q6W = 6-weekly dosing

2L = Second Line; AE(s) = Adverse Event(s); ALK = Anaplastic Lymphoma Kinase; CI = Confidence Interval; CNS = Central Nervous System; CR = Complete Response; DOR = Duration of Response; ECOG PS = Eastern Cooperative Oncology Group Performance Status; EGFR = Epidermal Growth Factor Receptor; HR = Hazard Ratio; ILD = Interstitial Lung Disease; irRC = Immune-Related Response Criteria; IV = intravenous; mDOR = Median Duration of Response; mo = months; n = number; no. = number; NR = Not Reported; NSCLC = Non-Small Cell Lung Cancer; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PD-L1 = Programmed Death-Ligand 1; PFS = Progression-Free Survival; Q3W = 3-weekly dosing; Q6W = 6-weekly dosing; R = Randomized; RECIST = Response Evaluation Criteria in Solid Tumors; SD = Stable Disease; TPS = Tumor Proportion Score; TRAEs = Treatment-Related Adverse Events; TTR = Time to Response; y = year

1. Herbst R, Garon E, Kim D, et al. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC. J Thorac Oncol. 2021;16(10):1718-1732.
2. SmPC KEYTRUDA^® 01/2022