Perioperative: neoadjuvant KEYTRUDA plus chemotherapy followed by adjuvant KEYTRUDA monotherapy

Prescribing Information [External link]

The efficacy and safety of KEYTRUDA were
investigated as perioperative treatment in early-stage NSCLC in…

KEYNOTE-671

…a Phase III, randomised, double-blind clinical study in 797 patients with resectable Stage II, IIIA or IIIB (N2)* NSCLC¹

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

*Tumour staging system as per AJCC 8th edition.¹

Licensed indication
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 non-small cell lung carcinoma at high risk of recurrence in adults.²

KEYNOTE-671 study design (ITT population)^1,3–5

Key eligibility criteria:

• Pathologically confirmed, resectable Stage II, IIIA or IIIB (N2) NSCLC as per AJCC 8th edition
• ECOG PS 0 or 1
• Able to undergo surgery
• Provision of tumour sample for PD-L1 evaluation*

Key exclusion criteria:

• Prior therapy with an anti-PD-1,  anti-PD-L1, or anti-PD-L2 agents, or agents targeting other co-inhibitory T-cell receptors
• ILD or pneumonitis requiring steroids

• Dual primary endpoints: EFS by investigator (as per RECIST v1.1) and OS^§
• Secondary endpoints: mPR and pCR per blinded independent pathology review, and safety

Stratification factors:

• Stage (II vs III)
• PD-L1 TPS <50% vs ≥50%*
• Histology (squamous vs non-squamous)
• Region (East Asia vs other)

Surgical details:

• KEYTRUDA arm: 92.0% (n=299/325) complete (R0) surgical resection; 78.8% lobectomies
• Placebo arm: 84.2% (n=267/317) complete (R0) surgical resection; 75.1% lobectomies

*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) combined with either gemcitabine (1000 mg/m² on Days 1 and 8 Q3W; for squamous histology only) or pemetrexed (500 mg/m² IV Q3W; for non-squamous histology only).^1
‡Radiotherapy was to be administered to participants with microscopic positive margins, gross residual disease or extracapsular nodal extension following surgery, and to participants who did not undergo planned surgery for any reason other than local progression or metastatic disease.^3
§One-sided alpha of 2.5% split between EFS and OS.¹ EFS defined as the time from randomisation to the first occurrence of local progression that precluded the planned surgery, unresectable tumour, progression or recurrence according to RECIST v1.1, by the investigator’s assessment, or death from any cause and OS defined as the time from randomisation to death from any cause.^1
¶mPR defined as ≤10% viable tumour cells in resected primary tumour and lymph nodes and pCR defined as the absence of residual invasive cancer in resected primary tumour and lymph nodes [ypT0/Tis ypN0]) as assessed on the basis of blinded, central examination by a pathologist.¹

KEYNOTE-671: OS in the ITT population (IA1, IA2 and 5-year exploratory analysis)^*3,4,6

Dual primary endpoint

Median follow-up: 25.2 months (IA1); 36.6 months (IA2); 60.4 months (5-year exploratory analysis)

Data cut-off date: 29 July 2022 (IA1); 10 July 2023 (IA2); 3 July 2025 (5-year exploratory analysis)

• At IA1, OS was not mature, but showed a favourable trend (HR: 0.73)³
  • Median OS was not reached in either treatment arm³
• At IA2, the prespecified interim analysis for OS, a statistically significant and clinically meaningful OS benefit was shown with perioperative KEYTRUDA⁴
  • OS HR was 0.72 (95% CI: 0.56–0.93); one-sided p=0.00517^†4, representing a 28% reduction in risk of death, with the upper CI below unit⁴
  • Median OS was not reached in the perioperative KEYTRUDA arm vs 52.4 months in the placebo arm⁴

5-year exploratory analysis: OS in the ITT population⁶

Adapted from Wakelee H, et al. ESMO 2025.⁶

• At the 5-year exploratory analysis, OS rates were 64.6% with KEYTRUDA vs 53.6% with placebo (HR=0.74; 95% CI, 0.59–0.92)⁶
• No statistical conclusions can be drawn from exploratory analyses. KEYNOTE-671 was not powered to detect differences in the treatment effect in these subgroups; therefore, no conclusions can be drawn

Statistical significance for OS was demonstrated at IA2, therefore OS was not formally tested during the 5-year exploratory analysis.^3,6

*OS was defined as time from randomisation to death from any cause.^3
†Significance boundary at IA2, one-sided p=0.00543.⁴

5-year exploratory analysis. Data cut-off: 3 July 2025. Median follow-up: 60.4 months.⁶
No conclusions can be drawn from exploratory analyses.

5-year exploratory analysis: OS in key ITT subgroups⁶

Adapted from Wakelee H, et al. ESMO 2025.⁶

The subgroup for PD-L1 TPS (<1% and 1–49%) and nodal status (N0, N1, and N2) were not prespecified in the Statistical Analysis Plan.⁷

KEYNOTE-671: EFS in the ITT population (IA1, IA2, 5-year exploratory analysis)^*1,4,6

Dual primary endpoint

Median follow-up: 25.2 months (IA1); 36.6 months (IA2); 60.4 months (5-year exploratory analysis)

Data cut-off date: 29 July 2022 (IA1); 10 July 2023 (IA2); 3 July 2025 (5-year exploratory analysis)

• At IA1, EFS benefit in the overall population was shown to be statistically significant and clinically meaningful¹
  • EFS HR was 0.58 (95% CI: 0.46–0.72); p<0.001¹
  • Median EFS was not reached in the perioperative KEYTRUDA arm and was 17 months in the placebo arm¹
• At IA2, with additional 11 months of follow-up, benefit was sustained with HR 0.59⁴
  • Median EFS was more than doubled, being 47.2 months with KEYTRUDA vs 18.3 months with placebo⁴
  • 3-year EFS was 54% with pembrolizumab vs 35% with placebo⁴

5-year analysis: EFS in the ITT population

Adapted from Wakelee H, et al. ESMO 2025.⁶

• At the 5-year exploratory analysis, EFS rates were 49.9% with KEYTRUDA vs 26.5% with placebo (HR=0.58; 95% CI, 0.48–0.69)⁶
• No statistical conclusions can be drawn from exploratory analyses. KEYNOTE-671 was not powered to detect differences in the treatment effect in these subgroups; therefore, no conclusions can be drawn

5-year exploratory analysis: EFS in key ITT subgroups⁶

Adapted from Wakelee H, et al. ESMO 2025.⁶

The subgroup for PD-L1 TPS (<1% and 1–49%) and nodal status (N0, N1, and N2) were not prespecified in the Statistical Analysis Plan.⁷

5-year exploratory analysis. Data cut-off: 3 July 2025. Median follow-up: 60.4 months.⁶
No conclusions can be drawn from exploratory analyses.

The safety profile of perioperative KEYTRUDA (plus chemotherapy) was consistent with the safety profiles of the individual components and no new safety signals were seen.^1–6

Treatment-related adverse events (TRAEs)

5-year exploratory analysis. Data cut-off: 3 July 2025. Median follow-up: 60.4 months.⁶
*There were four deaths in the KEYTRUDA arm (atrial fibrillation, immune-mediated lung disease, pneumonia and sudden cardiac death). There were three deaths in the placebo arm (acute coronary syndrome, pneumonia and pulmonary haemorrhage). There have been no new treatment-related deaths during IA2, IA3 or 5-year exploratory analysis since IA1.^4,5

The most common TRAEs (occurring in ≥10% of patients), across all treatment phases, in both KEYTRUDA and placebo groups (as-treated population)*

Treatment-related adverse events (TRAEs)

Adapted from Spicer JD, et al. 2024.⁸

• TRAEs were AEs considered by the investigator to be related to chemotherapy, KEYTRUDA and placebo.

The incidence and nature of immune-mediated adverse events (IMAEs) in the KEYTRUDA arm were consistent with previous reports.⁶

IMAEs and infusion reactions

5-year exploratory analysis. Data cut-off: 3 July 2025. Median follow-up: 60.4 months.⁶
*There was one death in the KEYTRUDA arm (pneumonitis). There have been no new treatment-related deaths during IA2, IA3 or 5-year exploratory analysis since IA1.^4–6

The most common TRAEs (occurring in ≥10% of patients), across all treatment phases, in both KEYTRUDA and placebo groups (as-treated population)*

Treatment-related adverse events (TRAEs)

Adapted from Spicer JD, et al. 2024.⁸

IMAEs and infusion reactions were based on a list of preferred terms intended to capture known risks of KEYTRUDA and were considered regardless of attribution to study treatment by the investigator.

Median follow-up was 36.6 months. Data cut-off date for IA2: 10 July 2023.⁴
*IA2 data. Equivalent data was not presented at 5-year exploratory analysis.⁴

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-671 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

Abbreviations

AE, adverse event; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EFS, event-free survival;
EGFR, epidermal growth factor receptor; HR, hazard ratio; IA, interim analysis; IHC, immunohistochemistry;
ILD, interstitial lung disease; IMAE, immune-mediated adverse event; ITT, intention-to-treat; IV, intravenous; mo, months; mPR, major pathological response; N2, involvement of the ipsilateral mediastinal and/or subcarinal lymph nodes;¹
NR, not reached; NSCLC, non-small cell lung cancer; OS, overall survival; pCR, pathological complete response;
PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PD-L2, programmed death-ligand 2; pN, pathological node involvement; Pt-CT, platinum-containing chemotherapy; Pts, patients; Q3W, every 3 weeks; Q6W, every 6 weeks; RECIST, Response Evaluation Criteria in Solid Tumours;
TPS, tumour proportion score; TRAE, treatment-related adverse event; WBC, white blood cell.

References

1. Wakelee H, et al. N Engl J Med 2023;389:491–503 (including protocol and supplementary materials).
2. KEYTRUDA Summary of Product Characteristics. MSD. Available at: https://www.medicines.org.uk/emc/product/2498. Accessed: August 2026.
3. Wakelee H, et al. KEYNOTE-671: Randomised, double-blind, Phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early-stage NSCLC. ASCO. 2–6 June 2023. Chicago, Illinois, USA. Abstract: LBA100.
4. Spicer JD, et al. Overall survival in the KEYNOTE-671 study of perioperative pembrolizumab for early-stage NSCLC. ESMO. 20–24 October 2023. Madrid, Spain. Abstract: LBA56.
5. Majem M, et al. ESMO I-O 2024. 11–13 December 2024. Geneva, Switzerland. Abstract: LBA3.
6. Wakelee H, et al. Presented at ESMO. 17–21 October 2025. Berlin, Germany. Oral presentation.
7. ClinicalTrials.gov. Protocol amendment 671-11. Approval date November 29, 2022. Available at: https://cdn.clinicaltrials.gov/large-docs/43/NCT03425643/Prot_SAP_000.pdf. Accessed August 2026.
8. Spicer JD, et al. Lancet 2024;404(10459):1240– 1252 (and supplementary appendix).

Supporting documentation

Prescribing Information [External link]

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