Drug Trials Snapshot: LUMISIGHT

How were the trials designed?

The efficacy and safety of LUMISIGHT for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during lumpectomy surgery in patients with breast cancer were evaluated in a randomized, multicenter, intra-patient controlled clinical trial. A total of 406 adult patients with confirmed invasive breast cancer, DCIS, or both received 1 mg/kg LUMISIGHT by intravenous injection two to six hours prior to imaging with the Lumicell Direct Visualization System (DVS) intraoperative imaging device. Among them, 357 patients underwent LUMISIGHT-guided imaging after completion of the SOC lumpectomy procedure. Patients who received neoadjuvant chemotherapy or radiotherapy prior to surgery were excluded from study. After the SOC lumpectomy was completed, the lumpectomy cavity was divided into six regions based on anatomic orientation and each region was imaged with the Lumicell DVS. When positive fluorescence signal was detected, the tissue was resected with a cavity shave procedure and the region was re-imaged. A maximum of two LUMISIGHT-guided shaves were obtained from a single region. Histopathology analysis of excised tissue served as the reference standard. The reference standard for cavity regions that did not have a LUMISIGHT-guided cavity shave or tissue from a second surgery was histopathological status of the corresponding outermost surface of the lumpectomy specimen or SOC cavity shave. Positive margins were defined as tumor on ink for invasive cancers (with or without DCIS) or within 2 mm of the linked margin for DCIS alone.

The mean age of patients was 62 years (range: 36 to 83 years). Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other. Distribution by ethnicity was 3% Hispanic or Latino, 94% not Hispanic or Latino, and 3% unknown or unreported. In the study group, 70% of patients had invasive ductal carcinoma (with or without DCIS), 20% had DCIS only, 10% had invasive lobular carcinoma (with or without DCIS), and <1% had both invasive ductal and invasive lobular carcinoma.

The study assessed the proportion of patients receiving LUMISIGHT who had residual breast cancer detected and removed using the Lumicell DVS after completion of SOC lumpectomy and the image-level performance of LUMISIGHT for detection of residual breast cancer in the lumpectomy cavity after completion of SOC lumpectomy.

Who participated in the trials?

Table 1. Baseline Demographics of CL0007

_{Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat; SD, standard deviatio}

What are the benefits of this drug (results of trials used to assess efficacy)?

CL0007 assessed the proportion of patients receiving LUMISIGHT who had residual breast cancer detected and removed using the Lumicell DVS after completion of SOC lumpectomy. There were 166 of 357 (46%) patients who had at least one LUMISIGHT-guided shave. A total of 27 of 357 patients had residual breast cancer confirmed by histopathology in at least one LUMISIGHT-guided shave (7.6%; 95% CI: 5.0%, 10.8%).

Table 2 shows sensitivity and specificity of LUMISIGHT for residual breast cancer after completion of SOC lumpectomy calculated from the 2,346 evaluable images in the study. Regions of the lumpectomy cavity from which LUMISIGHT-guided shaves were taken contributed more than one image to the analysis.

Table 2. Image-Level Performance of LUMISIGHT for Detection of Residual Breast Cancer in the Lumpectomy Cavity After Completion of Standard of Care Lumpectomy

_{Source: LUMISIGHT Prescribing Information
¹ Regions of the lumpectomy cavity from which LUMISIGHT-guided shaves were taken contributed more than one image.
² Sensitivity and specificity were calculated using a generalized estimating equation method to account for within-patient correlation. 
Abbreviations: CI, confidence interval; NA, not applicable}

A total of 155 of 357 (43%) patients had at least one false positive image, and 28 of 357 (8%) patients had at least one false negative image. Among the 166 patients with at least one LUMISIGHT-guided shave, the mean total LUMISIGHT-guided shave volume was 22 cm3 ±20 cm3, accounting for 20% ±15% of the total volume of resection.

After completion of SOC lumpectomy, prior to LUMISIGHT-guided tissue removal, 62 of 357 patients (17%) had at least one cancer-positive margin. After LUMISIGHT-guided surgery, 9 of these 62 (15%) patients changed to having all cancer-negative margins, and 2 of the remaining 295 (1%) patients changed from having all cancer-negative margins to having at least one cancer-positive margin.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 3. Efficacy Results by Age and Race

_{Source: Adapted from FDA Review
¹ Other includes American Indian or Alaska Native, Asian, Black or African America, Native Hawaiian or Pacific Islander, other, and unknown or not reported
Note: Tissue-level sensitivity and specificity were derived using exact confidence interval estimates.
Abbreviations: CI, confidence interva}

What are the possible side effects (results of trials used to assess safety)?

The safety of LUMISIGHT was evaluated in 726 patients who received a single dose of 1 mg/kg of LUMISIGHT. Among these 726 patients, 703 (97%) had breast cancer and 23 (3%) had other types of cancer. The mean age of the patients was 62 years (range: 36 years to 95 years), and 98% of them were female. Distribution by race was 82% White, 7% Black or African American, 6% Asian, and 5% other or unreported. Distribution by ethnicity was 3% Hispanic or Latino, 93% not Hispanic or Latino, and 4% unknown or unreported.

Adverse reactions occurring in ≥1% of patients receiving LUMISIGHT were hypersensitivity (1.4%, including anaphylaxis [4 out of 726]) and chromaturia (85%). Chromaturia resolved within 48 hours after administration in 93% of patients, with the longest time to resolution of 15 days.

Adverse reactions occurring in <1% of patients were skin discoloration after extravasation, nausea, dyspnea, pyrexia, and vomiting.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 4. Side Effects by Age, Safety Population

_{Source: Adapted from FDA Review
¹ Other includes American Indian or Alaska Native, Asian, Black or African America, Native Hawaiian or Pacific Islander, other, and unknown or not reported
Abbreviations: AE, adverse event; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific ar}

Table 5. Side Effects by Race, Safety Population

_{Source: Adapted from FDA Review
¹ Other includes American Indian or Alaska Native, Asian, Black or African America, Native Hawaiian or Pacific Islander, other, and unknown or not reported
Abbreviations: AE, adverse event; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm}