If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
Alimta ® (pemetrexed for injection)100 mg and 500 mg vials
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
The safety and efficacy of pemetrexed in combination with pembrolizumab and platinum chemotherapy was investigated in KEYNOTE-189 (NCT02578680), a randomized, multicenter, double-blind, active-controlled trial conducted in patients with previously untreated, metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations, regardless of PD-L1 tumor expression status.1
Patients were ineligible for the trial if they had
an autoimmune disease that required systemic therapy within 2 years of treatment
a medical condition that required immunosuppression, or
received >30 Gy of thoracic radiation within the prior 26 weeks.1
Patients were randomized in a 2:1 ratio to one of 2 treatment arms in the study.1
In the pembrolizumab-containing arm, patients received pemetrexed 500 mg/m2, pembrolizumab 200 mg, and investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min IV on day 1 of each 21-day cycle for 4 cycles followed by pemetrexed 500 mg/m2 and pembrolizumab 200 mg IV Q3W. Pemetrexed was administered after pembrolizumab and prior to platinum chemotherapy on day 1.1
In the placebo arm, patients received placebo, pemetrexed 500 mg/m2, and investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min IV on day 1 of each 21-day cycle for 4 cycles followed by placebo and pemetrexed 500 mg/m2 IV Q3W.1
Treatment with pemetrexed continued until progression of disease as determined by the investigator or unacceptable toxicity. Patients randomized to the placebo arm were offered pembrolizumab at the time of disease progression. A total of 85 patients in the placebo, pemetrexed, and chemotherapy arm received an anti-PD-1/PD-L1 monoclonal antibody at the time of disease progression.1
Efficacy Results of KEYNOTE-189
A significant improvement in OS and PFS was observed for patients randomized to the pemetrexed, pembrolizumab, and platinum chemotherapy arm compared with placebo, pemetrexed, and platinum chemotherapy1 (see Table 1. KEYNOTE-189 Survival and Response Summary ).
Table 1. KEYNOTE-189 Survival and Response Summary1
Abbreviations: BICR = blinded, independent central radiologic review; CR = complete response; DoR = duration of response; HR = hazard ratio; NR = not reached; ORR = overall response rate; OS = overall survival; PD-L1 = programmed death-ligand 1; PFS = progression-free survival; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors.
a Assessed by the BICR according to RECIST v1.1.
b Based on the stratified Cox proportional hazard model.
c Based on stratified log-rank test.
d Response: best objective response as confirmed CR or PR.
Figure 1. Kaplan-Meier Curve for Overall Survival in KEYNOTE-1891
= Alimta + pembrolizumab + platinum chemotherapy.
A+C = Alimta + platinum chemotherapy + placebo.
Safety Results of KEYNOTE-189
The median duration of exposure to pemetrexed was 7.2 months (range: 1 day to 1.7 years). The most common AEs of pemetrexed when administered in combination with pembrolizumab and platinum chemotherapy are shown in Table 2. Adverse Reactions Occurring in ≥20% of Patients in KEYNOTE-189 . Additional details regarding laboratory abnormalities that worsened from baseline as well as AEs that led to pemetrexed dose interruptions/discontinuations can be found in the prescribing information.1
Table 2. Adverse Reactions Occurring in ≥20% of Patients in KEYNOTE-1891
Abbreviation: NCI CTCAE = National Cancer Institute Common Toxicity Criteria for Adverse Events.
a Graded per NCI CTCAE version 4.03.
b Includes asthenia and fatigue.
c Includes genital rash, rash, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular.
Pemetrexed was discontinued for AEs in 23% of patients in the pemetrexed, pembrolizumab, and platinum arm. The most common AEs resulting in discontinuation of pemetrexed in this arm were acute kidney injury (3%) and pneumonitis (2%).1
Enclosed Prescribing Information
AE = adverse event
ALK = anaplastic lymphoma kinase
AUC = area under the curve
EGFR = epidermal growth factor receptor
Gy = gray
IV = intravenous
NSCLC = non-small cell lung cancer
OS = overall survival
PD-1 = programmed death-1
PD-L1 = programmed death-ligand 1
Pembrolizumab = KEYTRUDA® (pembrolizumab), Merck & Co., Inc.
PFS = progression-free survival
Q3W = every 3 weeks
Date of Last Review: January 28, 2019