For patients determined to do all they can, start with ALIMTA + KEYTRUDA® (pembrolizumab) with platinum.1
Who he is >> Disciplined, gets right to the point, has strong values
How he lives >> A doer, will try anything, lives for his family
What he wants >> To fight for every minute, no matter what
HIS CLINICAL STATUS
- Nonsquamous mNSCLC (stage IV)
- Programmed death-ligand 1 (PD-L1) positive (55%)
- Struggling with multiple symptoms
- Highly affected by tumor burden
- Typical age-related health issues
- Age: 62
- Eastern Cooperative Oncology Group (ECOG) score: 1
Indicated in combination with pembrolizumab (pembro) and platinum chemotherapy as an initial treatment for nonsquamous metastatic non-small cell lung cancer (mNSCLC)
Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.
Final KEYNOTE-189 analysis confirms:
Significant median OS, median PFS, and ORR improvement with the ALIMTA + KEYTRUDA® (pembrolizumab) with platinum regimen, which included induction and treatment beyond Cycle 4, vs ALIMTA with platinum.1-3
After induction in combination with platinum (cisplatin or carboplatin), continuing ALIMTA + KEYTRUDA was integral to the results seen in KEYNOTE-189.1
The phase III KEYNOTE-189 study included patients with all PD-L1 expression levels.
KEYNOTE-189 initial analysis data (median follow-up 10.5 months) (ITT population)1,2
- 12-month overall survival (OS) rates2: ALIMTA + KEYTRUDA with platinum: 69.2%; ALIMTA + placebo with platinum: 49.4%
Select Important Safety Information
ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed.
View Trial Design
ALIMTA + KEYTRUDA with platinum resulted in significantly longer survival and greater response than ALIMTA with platinum as confirmed by the final analysis of KEYNOTE-189.1-3
KEYNOTE-189 final analysis data (median follow-up 18.8 months)* (ITT population)3
Median OS (co-primary endpoint)
- Patients with OS events: ALIMTA + KEYTRUDA with platinum: 62.9%; ALIMTA + placebo with platinum: 79.1%
- 24-month OS rates3: ALIMTA + KEYTRUDA with platinum: 45.7%; ALIMTA + placebo with platinum: 27.3%
Median PFS (co-primary endpoint)
- Patients with PFS events: ALIMTA + KEYTRUDA with platinum: 82.2%; ALIMTA + placebo with platinum: 95.6%
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.
Final subgroup analyses of KEYNOTE-189:
The ALIMTA + KEYTRUDA with platinum regimen showed improvement in median OS, median PFS, and ORR across all PD-L1 levels - including ≥50% - vs ALIMTA with platinum.2,3
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.
KEYNOTE-189 final subgroup data (median survival follow-up 18.8 months)* (ITT population)
Median OS (PD-L1 TPS ≥50%†)
Median OS (PD-L1 TPS 1%-49%†)
- ALIMTA + KEYTRUDA with platinum (n=128): 21.8 months (95% CI: 17.7-25.6);
- ALIMTA + placebo with platinum (n=58): 12.1 months (95% CI: 8.7-19.4);
- HR=0.66 (95% CI: 0.46-0.96)
Median OS (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=0.51 (95% CI: 0.36-0.71)
Select Important Safety Information
Warnings and Precautions
Renal failure: ALIMTA can cause severe, and sometimes fata, 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 design1,2,4
- 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.
OS and PFS 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
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
- 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
Clinical adverse reactions for ALIMTA + KEYTRUDA with platinum (cisplatin or carboplatin)1,2
Clinical adverse reactions (ARs) occurring in ≥20% of patients in KEYNOTE-1891
- In KEYNOTE-189, 23.0% of patients (n=93/405) in the ALIMTA + KEYTRUDA with platinum group discontinued ALIMTA due to ARs 11.4% of patients (n=23/202) in the ALIMTA + placebo with platinum group1,5
- The most common clinical ARs resulting in discontinuation of ALIMTA in the ALIMTA + KEYTRUDA with platinum group were acute kidney injury (3%) and pneumonitis (2%)1
Select clinical ARs generally decreased over time when using the ALIMTA + KEYTRUDA with platinum regimen, which included maintenance.6
The select clinical ARs occurred at Grades 3-4 in ≥3% of patients in KEYNOTE-189. All grade rates of occurrence for those select ARs by cycle are shown below.
Select clinical ARs by cycle occurring in patients receiving ALIMTA + KEYTRUDA with platinum in KEYNOTE-189
After induction 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:
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 carboplatin groups)
- Patients received a median of 11 cycles of KEYTRUDA in the cisplatin group and 10 cycles in the carboplatin 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
Select Important Safety Inforamtion
Warnings and Precautions
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.
Lung cancer doesn’t attack in one way, so help him fight back in more than one way.1,4,8
ALIMTA + KEYTRUDA with platinum may help you attack nonsquamous mNSCLC two ways at once.
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
- 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.
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
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
Dose reductions for:
- ALIMTA in combination with KEYTRUDA and cisplatin or carboplatin
Recommended dosage modifications for adverse reactionsa
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
- ALIMTA (pemetrexed for injection) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.
- Gandhi L, et al. N Engl J Med. 2018;378(22):2078-2092.
- Rodríguez-Abreu D, Powell SF, Hochmair MJ, et al. Protocol-specified final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC. Poster presented at: American Society of Clinical Oncology (ASCO); May 29-31, 2020; Virtual Scientific Program.
- KEYTRUDA (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2020.
- Data on file, Eli Lilly and Company. DOF-PM-US-0005.
- Data on file, Eli Lilly and Company. DOF-PM-US-0098.
- Gandhi L, et al. N Engl J Med. 2018;378(22)(suppl):2078-2092.
- 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.