KEYTRUDA plus chemotherapy in non-squamous mNSCLC

Prescribing Information [External link]

The efficacy and safety of KEYTRUDA plus chemotherapy were assessed in previously untreated metastatic non-squamous NSCLC in…

KEYNOTE-189

…a randomised, multicentre, double-blind, active-controlled Phase III trial in 616 patients with previously untreated metastatic non-squamous NSCLC with no EGFR– or ALK-positive mutations.¹

During this trial, KEYTRUDA achieved the dual primary endpoints of OS and PFS – see below for more details.¹

Licensed indication
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first‑line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR– or ALK-positive mutations.²

KEYNOTE-189 study design¹

Key eligibility criteria:

• Pathologically confirmed Stage IV non-squamous NSCLC
• ECOG PS 0 or 1
• Provision of tumour sample for PD-L1 evaluation*

Key exclusion criteria:

• Prior therapy
• Symptomatic brain metastasis
• Pneumonitis requiring systematic steroids
• Sensitising EGFR or ALK mutations

• Dual primary endpoints: OS and PFS by investigator (as per RECIST v1.1)^¶
• Secondary endpoints: ORR, DOR and safety^||

Stratification factors:

• PD-L1 TPS ≥1% vs <1%*
• Platinum-based chemotherapy
  (cisplatin vs carboplatin)
• Smoking history (never vs former
  or current)

Subsequent anti-PD-L1 therapy:¹

• 58.4% (n=118) patients received subsequent anti-PD-L1 therapy, including on study crossover to second-course KEYTRUDA

^*PD L1 TPS was assessed at a central laboratory using PD-L1 IHC 22C3 pharmDx.^1
†Platinum-containing chemotherapy consisted of cisplatin (75 mg/m² Q3W) or carboplatin (AUC 5 mg/mL/min) plus pemetrexed (500 mg/m² Q3W), followed by pemetrexed (500 mg/m² Q3W).^1
‡Patients who had SD or better after 35 cycles of KEYTRUDA or stopped treatment after achieving CR and received ≥8 cycles of treatment, but then experienced PD could receive a second course of KEYTRUDA for 17 cycles (^~1 year) if they had not received new cancer therapy since the last dose of KEYTRUDA.³
KEYTRUDA is not reimbursed after two years of treatment as recommended by NICE and the SMC.^4,5
§Patients could crossover to KEYTRUDA monotherapy after PD per RECIST v1.1 by blinded independent central review.^3
¶OS was defined as the time from randomisation to death from any cause and PFS was was defined as the time from randomisation to disease progression, as assessed by blinded, independent central radiologic review, or death from any cause, whichever occurred first.^1
||ORR was defined as the percentage of patients with a confirmed complete or partial response, DOR was defined as the time from first documented complete or partial response to disease progression or death. Both ORR and DOR were assessed by blinded, independent central radiologic review.¹

KEYNOTE-189: OS in the ITT population (IA1 and 5-year analysis)^1,6

Dual primary endpoint

Median follow-up: 10.5 months (IA1); 64.6 months (5-year analysis)^1,6
Data cut-off date: 8 November 2017 (IA1); 8 March 2022 (5-year analysis)^1,6

• At IA1, KEYTRUDA demonstrated a superior OS benefit vs pemetrexed and platinum chemotherapy, with a 51% reduced risk of death¹
  • Median OS was not reached with KEYTRUDA vs 11.3 months with pemetrexed and platinum chemotherapy. HR was 0.49 (95% CI: 0.38–0.64), p<0.001

5-year exploratory analysis: OS in the ITT population⁶

• No statistical conclusions can be drawn from exploratory analyses

Adapted from Garassino MC, et al. 2023.⁶

• At the 5-year analysis, KEYTRUDA continued to provide improved OS vs placebo

KEYNOTE-189: PFS in the ITT population (IA1 and 5-year analysis)^*†1,6

Dual primary endpoint

Median follow-up: 10.5 months (IA1); 64.6 months (5-year analysis)^1,6
Data cut-off date: 8 November 2017 (IA1); 8 March 2022 (5-year analysis)^1,6

• At IA1, KEYTRUDA demonstrated a superior PFS benefit vs pemetrexed and platinum chemotherapy, with a 48% reduced risk of progression¹
  • Median PFS was 8.8 months with KEYTRUDA vs 4.9 months with pemetrexed and platinum
    chemotherapy. HR was 0.52 (95% CI: 0.43–0.64), p<0.001

5-year exploratory analysis: PFS in the ITT population⁶

• No statistical conclusions can be drawn from exploratory analyses

Adapted from Garassino MC, et al. 2023.⁶

• At the 5-year analysis:
  • KEYTRUDA continued to provide improved PFS vs placebo⁶
  • ORR was 48.3% (95% CI: 43.4–53.2) with KEYTRUDA vs 19.9% (95% CI: 14.7–26.0) with pemetrexed and platinum chemotherapy⁶
  • Median DOR (range) was 12.7 (1.1–68.3+) months with KEYTRUDA vs 7.1 (2.4–31.5) months with pemetrexed and platinum chemotherapy⁶
  • A trend in survival benefit was observed in each of the PD-L1 TPS subgroups, including the PD-L1 TPS <1% expressors⁶

*Kaplan-Meier estimate.^6
†Assessed using RECIST v1.1 by blinded, independent, central review.⁶

Summary of AEs in all treated patients (5-year update)⁶

Median follow-up: 64.6 months⁶
Data cut-off date: 8 March 2022⁶

KEYTRUDA had a generally manageable safety profile, and the frequency of AEs in combination with pemetrexed and platinum chemotherapy was comparable to previous studies. An increase in the frequency of immune-mediated AEs and infusion reactions was observed in patients who received 35 cycles of KEYTRUDA.^1,2,6

Adapted from Garassino MC, et al. 2023.⁶

*All deaths were previously reported in Rodriguez-Abreu D, et al. Ann Oncol 2021;32:881–895.^7,8
†Events considered regardless of attribution to treatment or immune relatedness by the investigator.⁸

AEs occurring in ≥15% of patients (5-year analysis)⁶

Garassino MC, et al. 2023.⁶

Assessment of regimens

The 200 mg Q3W (once every 3 weeks) regimen has been assessed in phase 2 and 3 registration studies across a multitude of indications of KEYTRUDA. An exposure-response evaluation, using modelling and simulation, led to the approval of the 400 mg Q6W (once every 6 weeks) dosing for monotherapy and combination therapy.²

From a microbiological point of view, the product, once diluted, should be used immediately. The diluted solution must not be frozen. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 7 days at 2˚C to 8˚C, or 12 hours at room temperature, unless dilution has taken place in controlled and validated aseptic conditions. If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use.²

For stability related enquiries please contact medicalinformationuk@msd.com

KEYNOTE-189 clinical data presentation

Prescribing Information (United Kingdom) [External link]

A guide to KEYTRUDA® (pembrolizumab) and how to manage immune-mediated adverse events

Prescribing Information (United Kingdom) [External link]

KEYTRUDA early-stage and advanced NSCLC indications:²

• KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with NSCLC who are at high risk of recurrence following complete resection and platinum-based chemotherapy
• KEYTRUDA, in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, is indicated for the treatment of resectable NSCLC at high risk of recurrence in adults
• KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic NSCLC in adults whose tumours express PD-L1 with a ≥50% TPS with no EGFR– or ALK-positive tumour mutations
• KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR– or ALK-positive mutations
• KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults
• KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR– or ALK-positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA
• Please consult the Summary of Product Characteristics for further information to minimise the risks associated with the use of KEYTRUDA before making prescribing decisions.

Abbreviations

AE, adverse event; ALK, anaplastic lymphoma kinase; AUC, area under the curve; CI, confidence interval; CR, complete response; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status;
EGFR, epidermal growth factor receptor; HR, hazard ratio; IA, interim analysis; IHC, immunohistochemistry;
IMAE, immune-mediated adverse event; ITT, intent to treat; IV, intravenous; mNSCLC, metastatic non-small cell lung carcinoma; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PD, progressive disease;
PD-L1, programmed death-ligand 1; PFS, progression free survival; Q3W, every 3 weeks; Q6W, every 6 weeks;
RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease; TPS, tumour proportion score.

References

1. Gandhi L, et al. N Engl J Med 2018;378:2078–2092 (and protocol).
2. KEYTRUDA Summary of Product Characteristics. MSD. Available at: https://www.medicines.org.uk/emc/product/2498/smpc. Accessed: September 2025.
3. Gray JE, et al. WCLC. 28–31 January 2021. Virtual. Poster: MK-3475.
4. National Institute for Health and Care Excellence. TA683: Pembrolizumab with pemetrexed and platinum chemotherapy for untreated, metastatic, non-squamous non-small-cell lung cancer. Available at: https://www.nice.org.uk/guidance/TA683. Accessed: September 2025. NICE guidance is prepared for the National Health Service in England, and is subject to regular review and may be updated or withdrawn. NICE has not checked the use of its content in this document to confirm that it accurately reflects the NICE publication from which it is taken.
5. Scottish Medicines Consortium. Pembrolizumab for untreated PD-L1 positive metastatic non-small-cell lung cancer. Available at: https://scottishmedicines.org.uk/medicines-advice/pembrolizumab-keytruda-fullsubmission-123917/. Accessed: September 2025.
6. Garassino MC, et al. J Clin Oncol 2023:1992–1998.
7. Rodriguez-Abreu D, et al. Ann Oncol 2021;32:881–895.
8. Garassino MC, et al. ESMO. 9–13 September 2022. Paris, France. Poster: 973MO.

Supporting documentation

Prescribing Information (United Kingdom) [External link]
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