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.

ALIMTA® (pemetrexed): Use With Pembrolizumab and Platinum Chemotherapy

ALIMTA (pemetrexed) is indicated in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations.

Detailed Information

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

Endpointa

Pemetrexed
Pembrolizumab
Platinum Chemotherapy
(N=410)

Placebo
Pemetrexed
Platinum Chemotherapy
(N=206)

OS (1° endpoint)

Patients with event, n (%)

127 (31)

108 (52)

Median in months (95% CI)

NR (NR-NR)

11.3 (8.7-15.1)

HRb (95% CI)

0.49 (0.38-0.64)

P valuec

<.0001

PFS (1° endpoint)

Patients with event, n (%)

244 (60)

166 (81)

Median in months (95% CI)

8.8 (7.6-9.2)

4.9 (4.7-5.5)

HRb (95% CI)

0.52 (0.43-0.64)

P valuec

<.0001

ORRd

ORR, % (95% CI)

48 (43-53)

19 (14-25)

CR, %

0.5

0.5

PR, %

47

18

P valuee

<.0001

DoR

Median in months (range)

11.2 (1.1+, 18.0+)

7.8 (2.1+, 16.4+)

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.

e Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy, and smoking status.

Figure 1. Kaplan-Meier Curve for Overall Survival in KEYNOTE-1891

A+P+C = 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

Adverse Reactiona

All Grades
(%)

Grade 3 or 4
(%)

All Grades
(%)

Grade 3 or 4
(%)

 

Pemetrexed
Pembrolizumab
Platinum Chemotherapy
(n=405)

Placebo
Pemetrexed
Platinum Chemotherapy
(n=202)

Gastrointestinal Disorders

Nausea

56

3.5

52

3.5

Constipation

35

1.0

32

0.5

Diarrhea

31

5

21

3.0

Vomiting

24

3.7

23

3.0

General Disorders and Administration Site Conditions

Fatigueb

56

12

58

6

Pyrexia

20

0.2

15

0

Metabolism and Nutrition Disorders

Decreased appetite

28

1.5

30

0.5

Skin and Subcutaneous Tissue Disorders

Rashc

25

2.0

17

2.5

Respiratory, Thoracic, and Mediastinal Disorders

Cough

21

0

28

0

Dyspnea

21

3.7

26

5

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

ALIMTA® (pemetrexed for injection), for intravenous use, Lilly

Reference

1. Alimta [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.

Glossary

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

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