Is Neoadjuvant Nivolumab Plus Chemotherapy Feasible for Resectable Diffuse Pleural Mesotheliomas?

Treatment with neoadjuvant nivolumab, pemetrexed, and platinum may allow more patients with diffuse pleural mesotheliomas (DPM) to undergo pleurectomy/decortication (P/D), according to the results of a prospective pilot study presented at the 2024 American Society of Clinical Oncology Annual Meeting.

The current standard of care in the perioperative space remains platinum pemetrexed followed by resection for operable and resectable disease, according to study presenter Michael Offin, MD, of Memorial Sloan Kettering Cancer Center.

This study included 22 patients with DPM who were deemed operable and resectable by a multidisciplinary team at Memorial Sloan Kettering. Patients received 2 cycles of neoadjuvant nivolumab, pemetrexed, and platinum followed by P/D. The primary objective was defined as attempted P/D within 30 days of the planned surgery date.

Of the 22 included patients, 19 underwent attempted P/D. Two patients had disease progression on the preoperative scan and 1 declined surgery. No patient experienced preoperative toxicity that precluded attempting P/D.

Of the 19 attempted P/D, 95% occurred within 30 days of the planned date. One patient required biopsy due to increase pleural thickness and was found to have a tumor flare; that patient underwent P/D at day 37.

With a median follow-up of 32 months, the median overall survival for the 19 patients who attempted P/D was 33.9 months. The median progression-free (PFS) survival was 14.0 months. However, Dr. Offin noted that patients could have physician’s choice of adjuvant therapy after resection, which does affect the researchers’ ability to speak to PFS after resection.

Sixteen patients had evaluable disease on perioperative imaging. Of these, 31% had an unconfirmed modified RECIST partial response.

The researchers used resection specimens to attempt to define pathologic response in this disease. Pathologic response was assessed by determining the average viable tumor percentage. One-quarter of resection specimens had ≤10% viable tumor, and there was no clear correlation with survival outcomes. Dr. Offin noted that pathologic response is still poorly defined in DPM and further prospective work is needed in this area.

Finally, Dr. Offin attempted to put these results in context with the recently released results of the MARS2 trial, which noted inferior OS and quality of life in patients assigned to P/D compared with no surgery. He mentioned that the study was well-designed “for the time and location it was conceived”, but had a high post-operative mortality compared to what one would expect at a high-volume center.

Reference

Offin M, Lavin Y, Zatzman M, et al. Feasibility and safety of neoadjuvant nivolumab and chemotherapy for resectable diffuse pleural mesotheliomas: Results of a prospective pilot study. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.