For patients determined to do all they can, start with ALIMTA + KEYTRUDA (pembrolizumab) with platinum.1

Who she is >> Disciplined, gets right to the point, has strong values

How she lives >> A doer, will try anything, lives for her family

Who she is >> To fight for every minute, no matter what

HER CLINICAL STATUS:

  • Nonsquamous mNSCLC (stage IV)
  • Programmed death-ligand 1 (PD-L1) positive (55%)
  • Chemotherapy-eligible
  • Struggling with multiple symptoms
  • Highly affected by tumor burden
  • Typical age-related health issues
  • Age: 62
  • Eastern Cooperative Oncology Group (ECOG) score: 1
Photo of a determined womanPhoto of a determined woman

Indicated in combination with pembrolizumab (pembro) and platinum chemotherapy as an initial treatment for nonsquamous metastatic non-small cell lung cancer (mNSCLC)

Initial and updated analyses of KEYNOTE-189 showed improved median OS, median PFS, and ORR results with ALIMTA + KEYTRUDA with platinum vs ALIMTA with platinum.1-3

The phase III KEYNOTE-189 study included patients with all PD-L1 expression levels.

KEYNOTE-189 initial analysis (median follow-up 10.5 months) (ITT population)1,2

Median overall survival (OS) (co-primary endpoint)

Median OS KM curve from the initial analysis of KEYNOTE-189, ITT population

12-month OS rate2

  • ALIMTA + KEYTRUDA with platinum 69.2%; ALIMTA + placebo with platinum: 49.4%

Number of patients with OS events observed with ALIMTA + KEYTRUDA with platinum: 127 (31%); number of patients with OS events observed with ALIMTA + placebo with platinum: 108 (52%)

CI=confidence interval; HR=hazard ratio; ITT=intention-to-treat; NE=not estimable; NR=not yet reached.

Median PFS, ORR, and median duration of response from KEYNOTE-189 initial analysis

Number of patients with PFS events observed with ALIMTA + KEYTRUDA with platinum: 244 (60%); number of patients with PFS events observed with ALIMTA + placebo with platinum: 166 (81%)

Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.

a Based on the stratified Cox proportional hazard model.

b Based on stratified log-rank test.

c PFS, ORR, and DoR were assessed by BICR.

d Response: Best objective response as confirmed complete response or partial response.

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

BICR=blinded independent central review; ORR=overall response rate; PFS=progression-free survival.

View Trial Design

Median OS, median PFS, and ORR results from an updated analysis of KEYNOTE-1891-3

KEYNOTE-189 updated non-prespecified analysis (median survival follow-up 18.7 months) (ITT population)

Updated non-prespecified analysis results from KEYNOTE-189 (median survival follow-up 18.7 months; median study follow-up 23.1 months) were not error-controlled nor adjusted for multiplicity across endpoints, and therefore not optimized to detect a statistically significant difference in OS, PFS, or ORR. Conclusions of a statistically significant difference in OS, PFS, or ORR must be based only on the previous prespecified, error-controlled analysis. The ALIMTA + KEYTRUDA with platinum first-line nonsquamous mNSCLC indication is based on the initial results of KEYNOTE-189.2

ALIMTA + KEYTRUDA with platinum showed improved median OS as compared to ALIMTA with platinum.1-3

Median OS (co-primary endpoint)

Median OS KM curve from the updated analysis of KEYNOTE-189, ITT population

12- and 24-month OS rates3

  • 12-month: ALIMTA + KEYTRUDA with platinum: 70.0%; ALIMTA + placebo with platinum: 48.1%
  • 24-month: ALIMTA + KEYTRUDA with platinum: 45.5%; ALIMTA + placebo with platinum: 29.9%

Number of patients with OS events observed with ALIMTA + KEYTRUDA with platinum: 52.0%; number of patients with OS events observed with ALIMTA + placebo with platinum: 69.9%

a Based on the stratified Cox proportional hazard model.

Select Important Safety Information

Contraindication

ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed.

ALIMTA + KEYTRUDA with platinum showed improved median PFS vs ALIMTA with platinum in an updated non-prespecified analysis.1-3

Median PFSa (co-primary endpoint)

Median PFS KM curve from the updated analysis of KEYNOTE-189, ITT population

Number of patients with PFS events observed with ALIMTA + KEYTRUDA with platinum: 74.1%; number of patients with PFS events observed with ALIMTA + placebo with platinum: 92.2%

a PFS was assessed by BICR.

b Based on the stratified Cox proportional hazard model.

An updated analysis of KEYNOTE-189 showed ORR improvement with ALIMTA + KEYTRUDA with platinum as compared to ALIMTA with platinum.1-3

ORRa,b (secondary endpoint)

Chart showing ORR results from an updated analysis of KEYNOTE-189, ITT population

a ORR was assessed by BICR.

b Response: Best objective response as confirmed complete response or partial response.

Select Important Safety Information

Warnings and Precautions

Myelosuppression and increased risk of myelosuppression without vitamin supplementation: ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. Prior to treatment with ALIMTA, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin B12 are also required prior to ALIMTA treatment. Folic acid and vitamin B12 supplementation should be continued during treatment and for 21 days after the last dose of ALIMTA as they may reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer ALIMTA until the ANC is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3. Permanently reduce ALIMTA in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles.


KEYNOTE-189 efficacy results by PD-L1 expression levels2,4,5

Initial exploratory analysis in PD-L1 TPS subgroups

The subgroup analyses in the KEYNOTE-189 trial were prespecified but were exploratory and not error-controlled or appropriately powered; therefore, treatment differences cannot be regarded as statistically significant.

The phase III KEYNOTE-189 study included patients with all PD-L1 levels.

Table showing efficacy results by PD-L1 levels in KEYNOTE-189 initial subgroup analysis

* The PD-L1 TPS was defined as the percentage of tumor cells with membranous PD-L1 expression.2

a PFS and ORR were assessed by BICR.

TPS=tumor proportion score.

KEYNOTE-189 updated non-prespecified analysis: Median OS results across all PD-L1 expression levels2,3

Updated non-prespecified analysis results from KEYNOTE-189 (median survival follow-up 18.7 months; median study follow-up 23.1 months) were not error-controlled nor adjusted for multiplicity across endpoints, and therefore not optimized to detect a statistically significant difference in OS, PFS, or ORR. Conclusions of a statistically significant difference in OS, PFS, or ORR must be based only on the previous prespecified, error-controlled analysis of the ITT population. The ALIMTA + KEYTRUDA with platinum first-line nonsquamous mNSCLC indication is based on the initial results of KEYNOTE-189.2

The phase III KEYNOTE-189 study included patients with all PD-L1 expression levels.

PD-L1 TPS ≥50%*

Median OS by PD-L1 expression level (≥50%) from the KEYNOTE-189 updated subgroup analysisMedian OS by PD-L1 expression level (≥50%) from the KEYNOTE-189 updated subgroup analysis

12- and 24-month OS rates2,3

  • 12-month: ALIMTA + KEYTRUDA with platinum: 73.3% ALIMTA + placebo with platinum: 48.6%
  • 24-month: ALIMTA + KEYTRUDA with platinum: 51.9%; ALIMTA + placebo with platinum: 39.4%
  • PD-L1 TPS 1%-49%*: ALIMTA + KEYTRUDA with platinum (n=128): 21.8 months (95% CI: 17.7-25.9); ALIMTA + placebo with platinum (n=58): 12.1 months (95% CI: 8.7-19.4); HR=0.62 (95% CI: 0.42-0.92)

    12-month OS rate: ALIMTA + KEYTRUDA with platinum: 71.7%; ALIMTA + placebo with platinum: 50.0%

    24-month OS rate: ALIMTA + KEYTRUDA with platinum: 44.3%; ALIMTA + placebo with platinum: 33.0%

  • PD-L1 TPS <1%*: ALIMTA + KEYTRUDA with platinum (n=127): 17.2 months (95% CI: 13.8-22.8); ALIMTA + placebo with platinum (n=63): 10.2 months (95% CI: 7.0-13.5); HR=0.52 (95% CI: 0.36-0.74)

    12-month OS rate: ALIMTA + KEYTRUDA with platinum: 63.4%; ALIMTA + placebo with platinum: 47.6%

    24-month OS rate: ALIMTA + KEYTRUDA with platinum: 38.5%; ALIMTA + placebo with platinum: 15.5%

* THE PD-L1 TPS was defined as the percentage of tumor cells with membranous PD-L1 expression.2

Select Important Safety Information

Warnings and Precautions

Renal failure: ALIMTA can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with ALIMTA. Withold ALIMTA in patients with a creatinine clearance of less than 45 mL/min.

KEYNOTE-189 study design1,2,6

  • The phase III KEYNOTE-189 study included patients with all PD-L1 levels
  • After initial therapy, ALIMTA and KEYTRUDA were continued until disease progression or unacceptable toxicity (or up to 35 cycles for KEYTRUDA)2

KEYNOTE-189 was a phase III, randomized, multicenter, double-blind, active-controlled study investigating the safety and efficacy of ALIMTA + KEYTRUDA with platinum chemotherapy (cisplatin or carboplatin) (n=410) vs ALIMTA + placebo with platinum chemotherapy (n=206) in previously untreated patients with nonsquamous mNSCLC.

Chart showing study design of KEYNOTE-189.

Primary endpoints

OS and PFS as assessed by BICR using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ

Secondary endpoints

ORR and duration of response as assessed by BICR using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ

Select patient characteristics

  • 49% age 65 years or older; median age 64 years (range 34 to 84)
  • 31% had tumor PD-L1 expression TPS <1% (negative)
  • 72% received carboplatin
  • 12% were never smokers

Exclusion criteria

  • Patients with autoimmune disease that required systemic therapy within 2 years of treatment
  • Patients with a medical condition that required immunosuppression
  • Patients who had received more than 30 Gy of thoracic radiation within the prior 26 weeks

ALK=anaplastic lymphoma kinase; AUC=area under the curve; EGFR=epidermal growth factor receptor;
IV=intravenous; R=randomization.

Clinical adverse reactions for ALIMTA + KEYTRUDA with platinum (cisplatin or carboplatin)1,2

Clinical adverse reactions occurring in ≥20% of patients in KEYNOTE-1891

Table showing adverse reactions from KEYNOTE-189.
  • In KEYNOTE-189, 23.0% of patients (n=93/405) in the ALIMTA + KEYTRUDA with platinum group discontinued ALIMTA due to adverse reactions vs 11.4% of patients (n=23/202) in the ALIMTA + placebo with platinum group1,7
  • The most common clinical adverse reactions resulting in discontinuation of ALIMTA in the ALIMTA + KEYTRUDA with platinum group were acute kidney injury (3%) and pneumonitis (2%)1

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.

NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

After 4 cycles in combination with platinum, continuing ALIMTA + KEYTRUDA was integral to the results seen in KEYNOTE-189.1

The uninterrupted treatment regimen in KEYNOTE-189 demonstrated significant improvements in OS, PFS, and ORR compared to continuous treatment with ALIMTA + placebo (including 4 platinum combination cycles).1,2

Dosing of ALIMTA, KEYTRUDA, and platinum (cisplatin or carboplatin) in KEYNOTE-189:

Graphic showing the dosing of ALIMTA + KEYTRUDA with platinum in KEYNOTE-189.

In KEYNOTE-1895:

The median number of cycles was similar between ALIMTA and KEYTRUDA.

  • Patients received a median of 9 cycles of ALIMTA (in both the cisplatin and carbo groups)
  • Patients received a median of 11 cycles of KEYTRUDA in the cisplatin group and 10 cycles in the carbo group

The percentage of patients who received ≥5 doses was similar between ALIMTA and KEYTRUDA.

  • 77% of patients in the ALIMTA + KEYTRUDA with platinum arm received ≥5 doses of ALIMTA
  • 79% of patients in the ALIMTA + KEYTRUDA with platinum arm received ≥5 doses of KEYTRUDA
More Dosing Information

Lung cancer doesn't attack in one way, so help her fight back in more than one way.1,6,8

ALIMTA + KEYTRUDA with platinum may help you attack nonsquamous mNSCLC two ways at once.

Graphic showing the two ways ALIMTA + KEYTRUDA with platinum helps fight NS mNSCLC

Fight cancer in two ways:

Disrupt cell replication

  • ALIMTA: A folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication
  • Platinum chemotherapy (carboplatin or cisplatin): Interferes with DNA repair, causes DNA damage, and disrupts cell replication

Reactivate T-cells

  • KEYTRUDA: Binds to the PD-1 receptor to block its interaction with PD-L1 and PD-L2 to help reactivate T-cells and restore anti-tumor immune response

ALIMTA + KEYTRUDA with platinum has the potential to attack healthy cells as well as tumor cells, which can be serious.

PD-1=programmed death protein 1, PD-L2=programmed death-ligand 2.

National Comprehensive Cancer Network® (NCCN®) recommendations for nonsquamous mNSCLC9

Table showing Category 1 recommendations from NCCN Guidelines for nonsquamous mNSCLC

† Category 1: Based on high-level evidence (eg, randomized phase III trials), there is uniform NCCN consensus that the intervention is appropriate.

FDA-Approved Indication1

ALIMTA is indicated in combination with pembrolizumab (pembro) and platinum chemotherapy for the initial treatment of patients with nonsquamous metastatic non-small cell lung cancer (mNSCLC) with no EGFR or ALK genomic tumor aberrations.

Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.

Combining ALIMTA + KEYTRUDA with platinum in 1st line may help you change outcomes without changing the dosing you may already know.*1,2

Dosing and administration for ALIMTA when used in combination with KEYTRUDA and cisplatin or carboplatin1

Table of dosing recommendations for ALIMTA + KEYTRUDA with cisplatin or carboplatin in first line.

Following completion of platinum-based therapy, treatment with ALIMTA (with or without KEYTRUDA) is administered until disease progression or unacceptable toxicity.

There is no recommended dose for patients whose creatinine clearance is less than 45 mL/min.

  • Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of ALIMTA and continuing until 21 days after the last dose of ALIMTA
  • Administer vitamin B12, 1 mg intramuscularly, 1 week prior to the first dose of ALIMTA and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with ALIMTA. Do not substitute oral vitamin B12 for intramuscular vitamin B12
  • Administer dexamethasone 4 mg orally twice daily for 3 consecutive days, beginning the day before each ALIMTA administration
  • In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided

NS=nonsquamous.

* This dosing recommendation is for patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater.

Dosing modifications1

Dose reductions for:

  • ALIMTA in combination with KEYTRUDA and cisplatin or carboplatin

Recommended dosage modifications for adverse reactionsa

Table showing dosing modifications for adverse reactions with ALIMTA.

Dosing modification notes

  • Obtain complete blood count on days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. Do not administer ALIMTA if the creatinine clearance is less than 45 mL/min
  • Delay initiation of the next cycle of ALIMTA until recovery of nonhematologic toxicity to grade 0-2, ANC is 1500 cells/mm3 or higher, and platelet count is 100,000 cells/mm3 or higher
  • Upon recovery, modify the dosage of ALIMTA in the next cycle as specified in the table above
  • For dosing modifications for cisplatin, carboplatin, and KEYTRUDA, refer to the respective prescribing information for each medication

a NCI CTCAE version 2.0.

References

  1. ALIMTA (pemetrexed for injection) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.
  2. Gandhi L, et al. N Engl J Med. 2018;378(22):2078-2092.
  3. Gadgeel S, Garassino MC, Esteban E, et al. KEYNOTE-189: Updated overall survival and progression after the next line of therapy with pembrolizumab plus chemotherapy with pemetrexed and platinum vs placebo plus chemotherapy for metastatic nonsquamous non-small-cell lung cancer. Poster presented at: ASCO Annual Meeting; June 2, 2019; Chicago, IL.
  4. Gandhi L. KEYNOTE-189: Randomized, double-blind, phase 3 study of pembrolizumab or placebo plus pemetrexed and platinum as first-line therapy for metastatic NSCLC. Presented at: AACR Annual Meeting; April 14-18, 2018; Chicago, IL.
  5. Gandhi L, et al. N Engl J Med. 2018;378(22)(suppl):2078-2092.
  6. KEYTRUDA (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2018.
  7. Data on file, Eli Lilly and Company. DOF-PM-US-0005.
  8. American Cancer Society website. How chemotherapy drugs work. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html. Accessed May 14, 2019.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2019. © National Comprehensive Cancer Network, Inc 2019. All rights reserved. Accessed September 19, 2019. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
Indications and Important Safety Information

Indications for ALIMTA® (pemetrexed for injection)

ALIMTA is indicated in combination with pembrolizumab (pembro) and platinum chemotherapy for the initial treatment of patients with nonsquamous metastatic non-small cell lung cancer (mNSCLC) with no EGFR or ALK genomic tumor aberrations.

ALIMTA is indicated in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).

ALIMTA is indicated as a single agent for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.

ALIMTA is indicated as a single agent for the treatment of patients with recurrent metastatic nonsquamous non-small cell lung cancer (NSCLC) after prior chemotherapy.

Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.

ALIMTA is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma (MPM) whose disease is unresectable or who are otherwise not candidates for curative surgery.

Important Safety Information

CONTRAINDICATION

ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed.

WARNINGS AND PRECAUTIONS

Myelosuppression and Increased Risk of Myelosuppression Without Vitamin Supplementation

ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation.

Prior to treatment with ALIMTA, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin B12 are also required prior to ALIMTA treatment. Folic acid and vitamin B12 supplementation should be continued during treatment and for 21 days after the last dose of ALIMTA as they may reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer ALIMTA until the ANC is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3. Permanently reduce ALIMTA in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles.

In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the ALIMTA arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.

Renal Failure

ALIMTA can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with ALIMTA.

The incidences of renal failure in clinical studies in which patients received ALIMTA with cisplatin were 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received ALIMTA as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI).

Withhold ALIMTA in patients with a creatinine clearance of less than 45 mL/min.

Bullous and Exfoliative Skin Toxicity

Serious and sometimes fatal, bullous, blistering, and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson Syndrome/toxic epidermal necrolysis, can occur with ALIMTA. Permanently discontinue ALIMTA for severe and life-threatening bullous, blistering, or exfoliating skin toxicity.

Interstitial Pneumonitis

Serious interstitial pneumonitis, including fatal cases, can occur with ALIMTA treatment. Withhold ALIMTA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue ALIMTA.

Radiation Recall

Radiation recall can occur with ALIMTA in patients who have received radiation weeks to years previously. Monitor patients for inflammation or blistering in areas of previous radiation treatment. Permanently discontinue ALIMTA for signs of radiation recall.

Increased Risk of Toxicity With Ibuprofen in Patients With Renal Impairment

Exposure to ALIMTA is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of ALIMTA. In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for ALIMTA adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity.

Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m2. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ALIMTA and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose.

DRUG INTERACTIONS

Ibuprofen increases exposure (AUC) of pemetrexed. In patients with creatinine clearance between 45 mL/min and 79 mL/min:

  • Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA.
  • Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided.

ADVERSE REACTIONS

Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with pembrolizumab and platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with platinum chemotherapy + placebo for initial treatment (KEYNOTE-189), respectively, were fatigue (12% vs 6%); diarrhea (5% vs 3%); dyspnea (3.7% vs 5%); vomiting (3.7% vs 3%); nausea (3.5% vs 3.5%); rash (2% vs 2.5%); decreased appetite (1.5% vs 0.5%); constipation (1% vs 0.5%); and pyrexia (0.2% vs 0%).

Common adverse reactions (all grades) occurring in ≥20% of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with pembrolizumab and platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with platinum chemotherapy + placebo for initial treatment (KEYNOTE-189), respectively, were nausea (56% vs 52%); fatigue (56% vs 58%); constipation (35% vs 32%); diarrhea (31% vs 21%); decreased appetite (28% vs 30%); rash (25% vs 17%); vomiting (24% vs 23%); cough (21% vs 28%); dyspnea (21% vs 26%); and pyrexia (20% vs 15%).

Severe adverse reactions (Grade 3-4) occurring in fully vitamin supplemented patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB), respectively, were neutropenia (15% vs 27%); fatigue (7% vs 5%); nausea (7% vs 4%); vomiting (6% vs 6%); anemia (6% vs 10%); thrombocytopenia (4% vs 13%); anorexia (2% vs 1%); creatinine elevation (1% vs 1%); diarrhea (1% vs 2%); stomatitis/pharyngitis (1% vs 0%); and constipation (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% fully vitamin supplemented patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB), respectively, were nausea (56% vs 53%); fatigue (43% vs 45%); vomiting (40% vs 36%); anemia (33% vs 46%); neutropenia (29% vs 38%); anorexia (27% vs 24%); constipation (21% vs 20%); stomatitis/pharyngitis (14% vs 12%); alopecia (12% vs 21%); diarrhea (12% vs 13%); thrombocytopenia (10% vs 27%); creatinine elevation (10% vs 7%), sensory neuropathy (9% vs 12%); taste disturbance (8% vs 9%); rash/desquamation (7% vs 8%); and dyspepsia/heartburn (5% vs 6%).

Severe adverse reactions (Grade 3-4) occurring in patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-ALIMTA containing, platinum-based induction therapy were anemia (3% vs 1%); neutropenia (3% vs 0%); fatigue (5% vs 1%); nausea (1% vs 1%); anorexia (2% vs 0%); infection (2% vs 0%); mucositis/stomatitis (1% vs 0%); diarrhea (1% vs 0%); and sensory neuropathy (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-ALIMTA containing, platinum-based induction therapy were fatigue (25% vs 11%); nausea (19% vs 6%); anorexia (19% vs 5%); anemia (15% vs 6%); increased rash/desquamation (10% vs 3%); ALT (10% vs 4%); sensory neuropathy (9% vs 4%); vomiting (9% vs 1%); increased AST (8% vs 4%); mucositis/stomatitis (7% vs 2%); neutropenia (6% vs 0%); diarrhea (5% vs 3%); and infection (5% vs 2%).

Severe adverse reactions (Grade 3-4) occurring in patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (PARAMOUNT), respectively, following ALIMTA plus cisplatin induction therapy were anemia (4.8% vs 0.6%); fatigue (4.5% vs 0.6%); neutropenia (3.9% vs 0%); nausea (0.3% vs 0%); and mucositis/stomatitis (0.3% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% patients with non-progressive locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus placebo as maintenance treatment (PARAMOUNT), respectively, following ALIMTA plus cisplatin induction therapy were fatigue (18% vs 11%); anemia (15% vs 4.8%); nausea (12% vs 2.4%); neutropenia (9% vs 0.6%); vomiting (6% vs 1.8%); mucositis/stomatitis (5% vs 2.4%); and edema (5% vs 3.6%).

Severe adverse reactions (Grade 3-4) occurring in fully supplemented patients with recurrent metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were neutropenia (5% vs 40%); fatigue (5% vs 5%); anemia (4% vs 4%); nausea (3% vs 2%); anorexia (2% vs 3%); vomiting (2% vs 1%); thrombocytopenia (2% vs 0%); increased ALT (2% vs 0%); increased AST (1% vs 0%); and stomatitis/pharyngitis (1% vs 1%).

Common adverse reactions (all grades) occurring in ≥5% of fully supplemented patients with recurrent metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were fatigue (34% vs 36%); nausea (31% vs 17%); anorexia (22% vs 24%); anemia (19% vs 22%); vomiting (16% vs 12%); stomatitis/pharyngitis (15% vs 17%); rash/desquamation (14% vs 6%); diarrhea (13% vs 24%); neutropenia (11% vs 45%); fever (8% vs 8%); thrombocytopenia (8% vs 1%); increased ALT (8% vs 1%); pruritus (7% vs 2%); increased AST (7% vs 1%); constipation (6% vs 4%); and alopecia (6% vs 38%).

Severe adverse reactions (Grade 3-4) occurring in fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving ALIMTA in combination with cisplatin versus cisplatin alone (JMCH), respectively, were neutropenia (23% vs 3%); nausea (12% vs 6%); vomiting (11% vs 4%); fatigue (10% vs 9%); thrombocytopenia (5% vs 0%); dehydration (4% vs 1%); anemia (4% vs 0%); diarrhea (4% vs 0%); stomatitis/pharyngitis (3% vs 0%); creatinine elevation (1% vs 1%); anorexia (1% vs 1%); constipation (1% vs 1%); dyspepsia (1% vs 0%); sensory neuropathy (0% vs 1%); rash (1% vs 0%); and creatinine clearance decrease (1% vs 2%).

Common adverse reactions (all grades) occurring in ≥5% of fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving ALIMTA in combination with cisplatin versus cisplatin alone (JMCH), respectively, were nausea (82% vs 77%); vomiting (57% vs 50%); neutropenia (56% vs 13%); fatigue (48% vs 42%); anemia (26% vs 10%); thrombocytopenia (23% vs 9%); stomatitis/pharyngitis (23% vs 6%); anorexia (20% vs 14%); diarrhea (17% vs 8%); creatinine clearance decreased (16% vs 18%); rash (16% vs 5%); constipation (12% vs 7%); creatinine elevation (11% vs 10%); alopecia (11% vs 6%); sensory neuropathy (10% vs 10%); conjunctivitis (5% vs 1%); dyspepsia (5% vs 1%); dehydration (7% vs 1%); and taste disturbance (8% vs 6%).

USE IN SPECIFIC PATIENT POPULATIONS

Lactation: There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from ALIMTA, advise women not to breastfeed during treatment with ALIMTA and for one week after the last dose.

Males of Reproductive Potential: ALIMTA may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use: The safety and effectiveness of ALIMTA in pediatric patients have not been established. Adverse reactions observed in pediatric patients studied were similar to those observed in adults.

Patients with Renal Impairment: ALIMTA is primarily excreted by the kidneys. Decreased renal function results in reduced clearance and greater exposure (AUC) to ALIMTA compared with patients with normal renal function. No dose is recommended for patients with creatinine clearance less than 45 mL/min.

Geriatric: The incidences of Grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials.

For safety and dosing guidelines for ALIMTA, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information.

PM_HCP_ISI_All_30JAN2019