Keytruda (pembrolizumab), a leading anti-PD-1 immuno-oncology drug, is making history in the treatment of lung cancer by expanding beyond the treatment of stage 4 non-small cell lung cancer (NSCLC) and redefining the concept of adjuvant, or "perioperative," therapy in patients with early-stage disease, experts said Thursday.

Such evaluations came at a media event organized by MSD Korea to celebrate the approval of Keytruda’s additional indications for adjuvant treatment of early-stage NSCLC.

Keytruda won approval last December for treating patients with resectable NSCLC as preoperative adjuvant therapy combined with platinum-based chemotherapy and as monotherapy as postoperative adjuvant therapy.

On May 14, Keytruda’s indication was expanded to include postoperative adjuvant therapy for patients with NSCLC who have undergone resection and platinum-based chemotherapy, further expanding the company's presence in early-stage lung cancer.

Professor Lee Se-hoon of the Department of Hematology-Oncology at Samsung Medical Center and Professor Kim Hong-kwan of the Department of Thoracic Surgery at SMC shared their latest perspectives on the clinical significance of pre- and postoperative adjuvant therapy based on the disease characteristics of early-stage lung cancer and Keytruda's approved clinical data.

In the first presentation, Professor Lee highlighted the unmet need for existing treatments for early-stage NSCLC and the clinical benefits identified in the KEYNOTE-671 and KEYNOTE-091 studies, which were the basis for Keytruda's approval in both indications.

"NSCLC is a high-risk cancer, even at early stages, with a greater likelihood than other cancers of recurrence or metastasis within five years of surgery," Professor Lee said. "It is also a cancer with a high disease burden, with five-year survival rates starting to decline in stage 1I and falling into the low 20s by stage 3.

Therefore, adjuvant chemotherapy has long been used to reduce the risk of recurrence and death after surgery. Still, its effectiveness has been modest, and there has always been an unmet clinical need to improve survival in early-stage patients, Lee added.

"Unlike breast cancer, where prior chemotherapy is not as effective and postoperative adjuvant chemotherapy is preferred, Keytruda has pioneered the concept of 'perioperative' therapy, where adjuvant chemotherapy is administered before and after surgery, in the setting of early-stage NSCLC."

Professor Lee also highlighted the clinical implications of improving event-free survival (EFS), a key endpoint in early-stage cancer research.

In the KEYNOTE-671 study, which evaluated the efficacy of Keytruda as pre- and postoperative adjuvant therapy in patients with stage 2-3B, Keytruda significantly improved the co-primary endpoints of overall survival (OS) and EFS compared to existing therapy. Compared to existing therapy, Keytruda reduced the risk of death by 28 percent (HR 0.72) and the risk of relapse by 41 percent (HR 0.59), regardless of PD-L1 expression.

"I think EFS is more important than OS in early-stage patients," Lee said. "EFS means that the patient is in remission unless an event occurs, and the difference between 'having the disease' and 'not having the disease' is palpable to the patient-facing physician."

Lee emphasized that EFS is a marker that can increase the chance of a cure. In the KEYNOTE-671 study, Keytruda reduced the risk of EFS by 41 percent, which is unprecedented data.

In addition, KEYNOTE-091, which evaluated KEYTRUDA as adjuvant therapy after surgery in patients with stage 1B-3A NSCLC, showed a reduced risk of recurrence regardless of PD-L1 expression, "which further supports the use of Keytruda after surgery and complements the results of KEYNOTE-671," Lee said

"Based on these results, international guidelines recommend Keytruda as the only treatment for the 'perioperative' treatment of early-stage NSCLC," Professor Lee said. "The news of approving Keytruda's indication this month, following last year, is significant in that Korean patients will be able to receive an immuno-oncology drug with proven therapeutic benefits."

In the second session titled "Clinical Significance of Perioperative Adjuvant Therapy in Patients with Operable Early Stage Lung Cancer from a Thoracic Surgery Perspective," Professor Kim explained the disease characteristics of surgically resectable early-stage lung cancer and the importance of pre- and postoperative adjuvant therapy in clinical practice.

In general, curative surgery is the standard treatment for stage 1-3 lung cancer. However, even for patients in this stage, some surgeries are not possible depending on the location of the tumor, including excessively large tumor size, superior vena cava invasion, or mediastinal lymph node infiltration, and the prognosis is poor even after surgical resection.

"Even for patients with early detection of lung cancer, it has been difficult to receive standard treatment due to inoperable tumor size and location," Professor Kim said. "However, with Keytruda upfront adjuvant therapy, we can now reduce tumor size and reduce micrometastases before surgery, opening up the possibility of effective treatment options for patients who were previously on the borderline for surgery."

Kim continued, "We believe that Keytruda-based adjuvant therapies, particularly perioperative adjuvant therapy, which is recommended as the global standard of care, can positively impact surgical outcomes as a preoperative upfront anticancer therapy and contribute to improved overall survival by reducing the risk of recurrence and thus reducing the risk of death.”