Neoadjuvant Anti-PD-1 Therapy Active in NSCLC

Patrick M. Forde, MBBCh

Almost 40% of patients with resected early-stage non—small cell lung cancer (NSCLC) had evidence of tumor regression following neoadjuvant treatment with nivolumab (Opdivo) in a preliminary clinical trial, according to data presented at the European Society for Medical Oncology (ESMO) conference in Copenhagen.

Seven of 18 evaluable patients had significant pathologic responses after 2 doses of the PD-1 inhibitor prior to surgery. Radiographic evidence of response occurred in 3 patients, all of whom had PD-L1 positive tumors.

The findings suggested that preoperative treatment with anti-PD-1 immunotherapy has potential to achieve tumor regression in a substantial portion of patients, Patrick M. Forde, MBBCh, reported at ESMO.

“Neoadjuvant nivolumab in patients with early stage lung cancer did not delay or interfere with surgical resection, and there were no safety signals,” said Forde, an assistant professor of oncology at Johns Hopkins Hospital in Baltimore, Maryland. “Major pathologic responses were associated with immune-cell infiltration of their tumors.

Comprehensive genomic, immunohistochemical, T-cell receptor clonality, and tumor infiltrating lymphocyte (TIL) functionality studies are ongoing. Larger follow-up clinical studies are planned, Forde added. Anti-PD-1 therapy has previously demonstrated efficacy in patients with advanced NSCLC, including improved survival in some cases. When it comes to adjuvant chemotherapy, most patients continue to do poorly and derive minimal benefit, even though resectable early lung cancer has a more favorable prognosis, Forde noted.

Neoadjuvant immunotherapy affords opportunities for performing related scientific analyses and assessment of pathologic response in cancer. Additionally, preoperative immunotherapy has the potential to enhance systemic immunity against occult metastases.

Investigators at Johns Hopkins and Memorial Sloan Kettering Cancer Center in New York collaborated in the preliminary clinical evaluation of neoadjuvant immunotherapy with nivolumab for patients with previously untreated early-stage, resectable NSCLC. Patients with stage I/IIIa disease received nivolumab 3 mg/kg infusions 28 and 14 days prior to surgery.

For patients with viable tumor tissue, investigators analyzed TILs and lymph node cells, and various laboratory parameters in blood specimens were performed. Patients received standard-of-care postoperative treatment. The safety follow-up covered the first 30 days after surgery.

The primary endpoints were safety and feasibility, as assessed during an initial 6-patient experience. Exploratory endpoints included correlative studies of blood and tumor tissue, pathologic response, relapse-free survival, and overall survival. Data analysis included 18 patients.

The study population had a median age of 68 and consisted of 9 men and 9 women. All but 1 patient had a smoking history. Two-thirds of the patient tumors had nonsquamous histology.

Administration of neoadjuvant nivolumab did not cause any delays in planned surgical resection. Safety data for 19 enrolled patients showed that 6 patients had treatment-related adverse events, all of which were consistent with previously reported clinical experience with nivolumab. One patient had a grade 3/4 adverse event, and 1 patient discontinued treatment because of adverse events.

During the safety evaluation, 1 patient died of a pulmonary embolism secondary to a fall and related head injury, and the death was judged unrelated to study treatment.

By radiographic RECIST criteria, four of 18 evaluable patients had partial responses, and 13 others had stable disease. Seven patients had pathologic downstaging, defined as less than 10% residual viable tumor at resection. One patient had a pathologic complete response.

The data yielded no genomic, histologic, or clinical predictors of pathologic response or nonresponse. Patients with and without major responses had sequence alterations and candidate biomarkers. Status as a current or former smoker was the one consistency.