Bottom line: Patients with resectable non-small cell lung cancer (NSCLC) who were treated with neoadjuvant nivolumab had improved five-year recurrence-free and overall survival rates compared with historical outcomes.

Journal through which the study was published: Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR)

Writer: The senior writer is Patrick Forde, MBBCh, an associate professor of oncology and director of the Thoracic Oncology Clinical Research Program on the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Samuel Rosner, MD, is co-first writer of the study and is a medical oncology fellow on the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a member of Forde’s research group.

Background: NSCLC is probably the most common kind of lung cancer and is a number one reason behind cancer-related death worldwide. Despite strides in treating metastatic NSCLC, recent treatments for earlier-stage disease have only recently emerged, based on Forde.

Rosner added that there’s great interest in optimizing neoadjuvant strategies for earlier-stage NSCLCs which can be eligible for surgical resection. Rosner is a medical oncology fellow on the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a member of Forde’s research group.

Forde, Rosner, and colleagues previously reported safety and efficacy results from a phase II clinical trial through which patients with stage I-III resectable NSCLC were treated with two doses of neoadjuvant nivolumab. Major pathological responses were observed in 45 percent of patients, independent of tumor PD-L1 expression, and 73 percent of patients whose tumors were surgically resected were recurrence-free 18 months following surgery.

The newest publication reports the ultimate analyses from this trial, including five-year recurrence-free and overall survival rates for the 20 patients who underwent surgical resection.

“To our knowledge, that is the longest follow-up up to now for a PD-1/PD-L1 inhibitor within the neoadjuvant setting for any solid tumor,” said Forde.

Results: Among the many 20 patients who underwent surgical resection, 12 patients (60 percent) remained recurrence-free five years after surgery, and 16 patients (80 percent) were alive, exceeding the 36 to 68 percent five-year survival rate historically observed for patients with stage I-III NSCLC, Rosner noted. Forde added that the observed patient outcomes after neoadjuvant nivolumab were higher than those historically observed amongst patients treated with neoadjuvant chemotherapy.

The authors also identified major pathologic response after neoadjuvant nivolumab as a possible predictive biomarker of recurrence-free and overall survival. Of the nine patients who had a significant pathological response after neoadjuvant nivolumab, eight were alive and cancer-free five years after treatment. One patient experienced a reoccurrence throughout the first 10 months after treatment but has since been disease-free after definitive chemoradiation. The one death on this subgroup was unrelated to cancer.

In contrast, six of the 11 patients who didn’t have a significant pathological response experienced disease reoccurrence, and three of those patients died resulting from their cancer. These results indicate that a significant pathological response following neoadjuvant nivolumab could also be related to a lower risk of disease reoccurrence and death, although the authors caution that these results are preliminary and require further validation in larger studies.

Neoadjuvant nivolumab didn’t result in surgical delays, and there was just one late-onset immune-related opposed event, which occurred 16 months after nivolumab treatment and was successfully managed, the authors noted.

Writer’s comments: “The outcomes from the five-year follow-up evaluation indicate that neoadjuvant nivolumab was secure in long-term follow-up and led to encouraging survival on this patient cohort,” said Forde. “The long-term safety and efficacy data from this study provide further support for using nivolumab within the neoadjuvant setting.”

Neoadjuvant nivolumab together with chemotherapy was approved by the U.S. Food and Drug Administration in March 2022 for the treatment of lung cancer. “Further studies will help us determine whether select patients may profit from immunotherapy alone,” Forde noted.

“An interesting finding from the evaluation was the difference in outcomes between patients with and and not using a major pathological response,” said Rosner. “Although the sample size was small, the outcomes illustrate the potential power of pathological response as a predictive biomarker.”

Study limitations: Limitations of the study include the small cohort size and the single-arm design.

Funding & disclosures: The study was supported by funding from Stand Up To Cancer (AACR is the Scientific Partner of Stand Up To Cancer), Bristol-Myers Squibb, the International Immuno-Oncology Network, the LUNGevity Foundation, the International Association for the Study of Lung Cancer, the Prevent Cancer Foundation, the Lung Cancer Foundation of America, the MacMillan Foundation, the ECOG-ACRIN Cancer Research Group, the National Institutes of Health, Johns Hopkins University Cancer Center, and Memorial Sloan Kettering Cancer Center.

Source:

American Association for Cancer Research

Journal reference:

Rosner, S., et al. (2023) Five-12 months Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non-Small Cell Lung Cancer. Clinical Cancer Research. doi.org/10.1158/1078-0432.CCR-22-2994.