ALIMTA/carbo + pembro is the first chemotherapy/immunotherapy combination approved in 1st line for patients with nonsquamous mNSCLC.1

National Comprehensive Cancer Network® (NCCN®) recommendation2

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Category 1*

First line: Pemetrexed for injection (ALIMTA) in combination with carboplatin (carbo) and pembrolizumab (pembro) is recommended as a first-line treatment option for patients with advanced or metastatic nonsquamous NSCLC.†,§ Pemetrexed is not recommended for squamous cell histology.

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

† For patients with negative or unknown test results for EGFR, ALK, ROS1, and BRAF.

§ For patients with PD-L1 <50% or unknown test results.

ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; PD-1=programmed death-1; PD-L1=programmed death-ligand 1.

FDA-Approved Indication

ALIMTA is indicated in combination with carboplatin (carbo) and pembrolizumab (pembro) for the initial treatment of patients with nonsquamous metastatic non-small cell lung cancer (mNSCLC). This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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

40%-50% of patients won't receive second-line therapy; ALIMTA/carbo + pembro may help  improve outcomes in first-line compared to ALIMTA/carbo alone

In KEYNOTE-021G, patients who received ALIMTA/carbo + pembro experienced nearly double the overall response rate (ORR) and over 1 year of median progression-free survival (PFS) compared to 8.9 months with ALIMTA/carbo alone.1,7

A chance to nearly double the ORR in patients with nonsquamous mNSCLC, with or without PD-L1 expression

Primary endpoint: ORRa in KEYNOTE-021 (Cohort G1)

Overall response rate results for ALIMTA/carbo + pembro in nonsquamous metastatic NSCLC

Secondary endpoints (N=123)

Median PFSa (months) (95% CI)

ALIMTA/carbo + pembro (n=60): 13.0 (8.3-NE); ALIMTA/carbo alone (n=63): 8.9 (4.4-10.3); HRc (95% CI)=0.53 (0.31-0.91); P=0.020d

Duration of response

93% of responders had response duration ≥6 monthse with ALIMTA/carbo + pembro (n=60) (range 1.4+ to 13.0+ months) vs 81% with ALIMTA/carbo alone (n=63) (range 1.4+ to 15.2+ months)

In exploratory subgroup analyses stratified by PD-L1 status (TPS <1% and TPS ≥1%), ORR was similar across PD-L1 expression with ALIMTA/carbo + pembro.f,1,8

  • ORR in PD-L1 tumor expression subgroups with ALIMTA/carbo + pembro
    • TPS ≥1%: 54% (95% CI: 37-70; n=21/39) and TPS <1%: 57% (95% CI: 34-78; n=12/21)
  • ORR in PD-L1 tumor expression subgroups with ALIMTA/carbo
    • TPS ≥1%: 38% (95% CI: 23-54; n=15/40) and TPS <1%: 13% (95% CI: 3-34; n=3/23)
  • 36% of patients in the trial (n=44/123) had tumor PD-L1 expression TPS <1%1
  1. ORR and PFS were assessed by BICR using RECIST 1.1.
  2. Based on Miettinen-Nurminen method stratified by PD-L1 status (TPS <1% vs TPS ≥1%).
  3. Based on the Cox proportional hazard model stratified by PD-L1 status (TPS <1% vs TPS ≥1%).
  4. Based on the log-rank test stratified by PD-L1 status (TPS <1% vs TPS ≥1%).
  5. Based on Kaplan-Meier estimation.
  6. Data based on exploratory analyses conducted in subgroups defined by the stratification variable, PD-L1 tumor expression (TPS <1% and TPS ≥1%).

BICR=blinded independent central review; CI=confidence interval; HR=hazard ratio; NE=not estimable; RECIST=Response Evaluation Criteria in Solid Tumors; TPS=tumor proportion score.

Select Important Safety Information

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

View Trial Design

Median PFS exceeded 1 year in KEYNOTE-021 (Cohort G1) in patients with nonsquamous mNSCLC who received ALIMTA/carbo + pembro.1,7

Median PFSa (months) (95% CI) in KEYNOTE-021 (Cohort G1)

Progression-free survival results for ALIMTA/carbo + pembro in nonsquamous metastatic NSCLC
  • Number of events observed with ALIMTA/carbo + pembro: 23 (38%) (15 patients [25%] with progressive disease and 8 deaths [13%])
  • Number of events observed with ALIMTA/carbo alone: 33 (52%) (27 patients [43%] with progressive disease and 6 deaths [10%])
  • Population included patients with nonsquamous mNSCLC, regardless of tumor PD-L1 status and no prior systemic treatment for metastatic disease
  1. PFS was assessed by BICR using RECIST 1.1.
  2. Based on the Cox proportional hazard model stratified by PD-L1 status (TPS <1% vs TPS ≥1%).
  3. Based on the log-rank test stratified by PD-L1 status (TPS <1% vs TPS ≥1%).

KEYNOTE-021 (Cohort G1) study design1,7

KEYNOTE-021 was an open-label, multicenter, multi-cohort study investigating the efficacy of ALIMTA/carbo + pembro (n=60) vs ALIMTA/carbo alone (n=63).

Trial design for ALIMTA/carbo + pembro in nonsquamous metastatic NSCLC

Patient characteristics

  • 97% of all patients had metastatic disease
  • 36% of all patients had tumor PD-L1 expression TPS <1%

Exclusion criteria

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

Primary endpoint

  • ORR as assessed by BICR using RECIST 1.1

Secondary endpoints

  • PFS as assessed by BICR using RECIST 1.1
  • Duration of response
  • Overall survival (OS)

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

AUC=area under the curve; IV=intravenous; NSCLC=non-small cell lung cancer; Q3W=every 3 weeks; R=randomization

The number of patients who discontinued ALIMTA because of adverse reactions was similar between ALIMTA/carbo + pembro and ALIMTA/carbo alone.1,9

In KEYNOTE-021 (Cohort G1)

Discontinuation rate due to adverse reactions in ALIMTA/carbo + pembro vs ALIMTA/carbo
  • The most common adverse reaction resulting in discontinuation of ALIMTA (≥2%) was acute kidney injury (3.4%). Adverse reactions leading to interruption of ALIMTA occurred in 36% of patients; the most common (≥2%) were fatigue (9%), neutrophil count decreased (9%), anemia (7%), dyspnea (3.4%), and pneumonitis (3.4%)1

KEYNOTE-021 was not designed to demonstrate a statistically significant difference in adverse reactions between study arms for any specified reaction listed.1

Adverse reactions occurring in ≥20% of patients in KEYNOTE-021 (Cohort G1)

Safety profile for ALIMTA/carbo + pembro in nonsquamous metastatic NSCLC
  1. Graded per NCI CTCAE version 4.0.
  2. Includes rash, rash generalized, rash macular, rash maculo-papular, and rash pruritic.

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

With ALIMTA/carbo + pembro in first line, you can still offer your patients who achieve stable disease or better the opportunity to continue treatment with ALIMTA maintenance.

85% of patients in the ALIMTA/carbo + pembro arm went on to receive maintenance therapy

In the KEYNOTE-021 (Cohort G1) study, 85% of patients in the ALIMTA/carbo + pembro arm (n=50) went on to receive ALIMTA maintenance therapy vs 69% in the ALIMTA/carbo arm (n=43).7

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.1

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

Dosing and administration for ALIMTA when used in combination with carbo and pembro in the treatment of nonsquamous mNSCLC1

Pembro should be administered prior to ALIMTA and carbo when given on the same day.

  • The recommended dose of ALIMTA when administered with carbo and pembro for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous (IV) infusion over 10 minutes prior to carboplatin on day 1 of each 21-day cycle for 4 cycles. Following completion of platinum-based therapy, ALIMTA may be administered as maintenance therapy, alone or with pembro, until disease progression or unacceptable toxicity. Pembro should be administered prior to ALIMTA when given on the same day
  • Please refer to the full prescribing information for pembrolizumab and for carboplatin
Dosing table for ALIMTA/carbo + pembro in nonsquamous metastatic NSCLC

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

  • 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
  • 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

NS=nonsquamous.

Dosing modifications1

Dose reductions for:

  • ALIMTA in combination with carbo and pembro
  • ALIMTA in combination with cisplatin
  • ALIMTA as a single agent

Recommended dosage modifications for adverse reactionsa

Dose reduction table for ALIMTA
  1. NCI CTCAE version 2.0.

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 carboplatin, pembrolizumab, and cisplatin, refer to the respective prescribing information for each medication
References
  1. ALIMTA (pemetrexed for injection) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2018. © National Comprehensive Cancer Network, Inc 2018. All rights reserved. Accessed June 27, 2018. 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.
  3. Scagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.
  4. Pirker R, et al. Lancet. 2009;373(9674):1525-1531
  5. Sandler A, et al. N Engl J Med. 2006;355(24):2542-2550.
  6. Stinchcombe TE, Socinski MA. J Thorac Oncol. 2009;4(2):243-250.
  7. Langer CJ, et al. Lancet Oncol. 2016;17(11):1497-1508.
  8. Langer CJ, et al. Lancet Oncol. 2016;17(11)(suppl):1497-1508.
  9. Data on file, Eli Lilly and Company. DOF-PM-US-0004.
Indications and Important Safety Information

Indications for ALIMTA® (pemetrexed for injection)

ALIMTA is indicated in combination with carboplatin (carbo) and pembrolizumab (pembro) for the initial treatment of patients with nonsquamous metastatic non-small cell lung cancer (mNSCLC). This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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 (grades 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 (grades 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 (grades 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 (grades 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 (grades 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%).

Severe adverse reactions (grades 3-4) occurring in patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA and carboplatin in combination with pembrolizumab versus ALIMTA and carboplatin for initial treatment (KEYNOTE-021), respectively, were fatigue (3.4% vs 0%); dyspnea (3.4% vs 0%); nausea (1.7% vs 0%); vomiting (1.7% vs 0%); diarrhea (1.7% vs 1.6%); rash (1.7% vs 1.6%); constipation (0% vs 1.6%); headache (0% vs 1.6%); and arthralgia (0% vs 1.6%).

Common adverse reactions (all grades) occurring in ≥20% of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA and carboplatin in combination with pembrolizumab versus ALIMTA and carboplatin for initial treatment (KEYNOTE-021), respectively, were fatigue (71% vs 50%); nausea (68% vs 56%); constipation (51% vs 37%); rash (42% vs 21%); vomiting (39% vs 27%); dyspnea (39% vs 21%); diarrhea (37% vs 23%); decreased appetite (31% vs 23%); headache (31% vs 16%); cough (24% vs 18%); dizziness (24% vs 16%); insomnia (24% vs 15%); pruritus (24% vs 4.8%); peripheral edema (22% vs 18%); dysgeusia (20% vs 11%); alopecia (20% vs 3.2%); upper respiratory tract infection (20% vs 3.2%); and arthralgia (15% vs 24%).

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 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.

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