KEYNOTE-671: Perioperative Use in Resectable NSCLC
Keytruda (pembrolizumab) plus chemotherapy before and after surgery cut the risk of death by 28% versus chemotherapy alone in patients with early-stage non-small cell lung cancer (NSCLC). Median overall survival was not reached in the Keytruda arm after about 25 months, compared to 52 months in the placebo group. Event-free survival hazard ratio was 0.58.[1][2]
KEYNOTE-859: First-Line Gastric/GEJ Cancer
In HER2-negative advanced gastric or gastroesophageal junction cancer, Keytruda plus chemotherapy improved overall survival to 12.9 months from 11.5 months with chemo alone (hazard ratio 0.78). Progression-free survival rose to 6.9 months from 5.6 months.[1][3]
KEYNOTE-966: Metastatic Pancreatic Cancer
Keytruda combined with chemotherapy extended overall survival to 10.6 months versus 9.9 months alone in metastatic pancreatic adenocarcinoma (hazard ratio 0.82), marking the first frontline immunotherapy approval in this setting.[1][4]
KEYNOTE-522: Triple-Negative Breast Cancer
Neoadjuvant Keytruda plus chemo followed by adjuvant Keytruda achieved pathologic complete response in 65% of patients, versus 56% with chemo alone. Event-free survival at 36 months was 84.5% versus 76.8%.[1][5]
KEYNOTE-564: Renal Cell Carcinoma
Adjuvant Keytruda after surgery reduced disease recurrence or death risk by 32% in high-risk clear cell renal cell carcinoma (hazard ratio 0.68). Median disease-free survival was not reached versus 24.1 months.[1][6]
Emerging Data in Melanoma and MSI-High Tumors
In advanced melanoma, Keytruda's KEYNOTE-006 trial showed 5-year overall survival of 34% as monotherapy, rising to 52% with ipilimumab combo. For MSI-high/dMMR solid tumors, objective response rate hit 33% with durable responses up to 4 years.[1][7]
Safety Profile Across Trials
Grade 3+ adverse events occurred in 44-78% of Keytruda arms, mainly from chemo combos, versus 34-66% in controls. Immune-related events like hypothyroidism (15-20%) and pneumonitis (3-5%) remain consistent; discontinuation rates around 10-20%.[1][2][3]
[1]: FDA Approvals for Pembrolizumab
[2]: NEJM: KEYNOTE-671
[3]: Lancet: KEYNOTE-859
[4]: NEJM: KEYNOTE-966
[5]: NEJM: KEYNOTE-522 Update
[6]: NEJM: KEYNOTE-564
[7]: Merck Press Release: Melanoma 5-Year Data