Thoracic: Lung Cancer: Clinical Trial: Evolving Technology
Pafolacianine for intraoperative molecular imaging of cancer in the lung: The ELUCIDATE trial

Read at the 102nd Annual Meeting of The American Association for Thoracic Surgery, Boston, Massachusetts, May 14-17, 2022.
https://doi.org/10.1016/j.jtcvs.2023.02.025Get rights and content

Abstract

Objective

The study objective was to determine the clinical utility of pafolacianine, a folate receptor–targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization.

Methods

In this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation.

Results

No drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging–discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease).

Conclusions

Intraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.

Graphical abstract

Methods, results, and implications are presented in a single graphical abstract.

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Section snippets

Trial Design and Oversight

Before surgery, participants were randomized to undergo white light plus IMI or white light only (10:1 ratio, as requested by the Food and Drug Administration). The assignment for imaging was revealed during surgery but only after completion of the white light evaluation and before IMI. The purpose of the 10:1 nonstratified permuted block randomization was only to reduce the risk of potential bias from underestimating the number of lesions localized first with white light if knowing that NIR

Characteristics of the Participants

The Consolidated Standards of Reporting Trials flow diagram is presented in Figure 3. Among 140 patients screened for eligibility, 24 were screen failures and 4 of the remaining 116 randomized participants were discontinued during the screening period before receiving an infusion of the study drug, and 1 additional participant withdrew consent because of an infusion reaction. Demographic characteristics of participants in the FS (N = 112), which includes the 1 participant who received the

Discussion

Pafolacianine represents a first-in-class agent to aid the surgeon in visualizing otherwise undetectable tumors and in determining tumor to resection margin distance.20,22 It offers the possibility of improving outcomes of cancer surgery by enabling surgeons to better identify primary tumors, detect occult synchronous lesions, and ensure adequate margins of resection. The technology is adjunctive to, rather than a replacement for, current preoperative imaging and intraoperative clinical

Conclusions

The use of IMI with pafolacianine represents a significant potential advancement over white light visualization alone by enhancing the intraoperative localization of presumed cancerous nodules, improving the ability to remove them with clean margins, and reducing the probability of leaving malignant tissue behind.

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  • The ELUCIDATE Study Group: Michael I. Ebright, MD, Columbia University Medical Center; Sidharta Peña Gangadharan, MD, Beth Israel Deaconess Medical Center; Brian E. Louie, MD, Swedish Cancer Institute and Medical Center; Sudish C. Murthy, MD, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Kalpaj R. Parekh, MBBS, University of Iowa Carver College of Medicine; Rishindra M. Reddy, MD, University of Michigan Medical School; Benny Weksler, MD, Allegheny General Hospital.

    Funding for this study was provided by On Target Laboratories, Inc.

    Advarra Institutional Review Board approval November 25, 2019, #Pro00040361.

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