We identified 11 patients with mPPGL who met inclusion criteria, and their baseline characteristics prior to starting lenvatinib are outlined in Table 1. Seven (63%) were male, and average age was 56 years (range, 44–69 years). No patient had an additional preexisting primary malignancy of a different organ. Most patients' primary tumor involved a paraganglioma (82%) and most were located in the abdomen (73%); other primary sites of disease included the neck, chest, and bladder with 1 person each. Seven (63%) had secretory disease, 5/11 (45%) had a germline mutation (all involving SDHB, though specific sequence alteration was not reported). Due to small numbers and other confounding variables, differences between SDHB-mutated and wild-type were not analyzed.
All but 1 patient had previously undergone surgery to remove the primary tumor; there was complete resection (R0) in 8/10 patients. The most common site of metastasis was to lymph nodes and/or bone (90.9%), followed by liver and peritoneum (54.5%), lung (45.5%), bladder and recurrent disease within the postsurgical adrenal bed (18.2%), and paravaginal (9.1%). Seven patients previously received radiotherapy. Five patients had received MIBG treatment previously. All patients received prior cytotoxic chemotherapy in the form of cyclophosphamide, vincristine, and dacarbazine, plus or minus octreotide. Only 2 patients were previously treated with an MKI, both treated with pazopanib. Most patients had bony involvement and received bone modulating therapy (zoledronic acid or denosumab). The ECOG status was primarily 0 or 1.
Of the 11 patients, 8 had measurable disease. Among the 8 patients, the ORR was 63%. Five patients demonstrated a PR to lenvatinib, and 3 patients had stable disease. There were no complete responses. The remaining 3 had unmeasurable disease though had less avidity on PET (Figure 1). Data on biochemical response was not available for all patients, although there was a trend in overall reduction of metanephrines/normetanephrines.
Change in tumor size. Out of 11 patients, 8 had measurable disease. 5/8 achieved a partial response (PR), and 3 patients had stable disease (SD), defined by RECIST 1.1.
At 12 months, 58.4% (95% CI, 22.7%-82.3%) of patients remained on treatment; median treatment duration was 14.7 months (95% CI, 2.3-NE) (Figure 2). The OS at 12 months was 80.8% (95% CI, 42.3%-94.9%) but median OS was not reached (Figure 3). Median PFS was 14.7 months (95% CI, 1.7-NE); PFS was 71.6% (95% CI, 35%-89.9%) at 6 months and 61.4% (95% CI, 26.6%-83.5%) at 12 months (Figure 4).
Median treatment duration. Median time from initiation of lenvatinib to discontinuation or date of last follow-up was 14.7 months.
All but 1 patient required a dose reduction. As expected, the most common AE was hypertension, as seen in 9/11 patients, and required adjustment of their antihypertensive therapy. Other side effects, as seen with other VEGF inhibitors, included anemia, fatigue, cough, proteinuria, nausea, vomiting, and weight loss. Our population did not develop oral mucositis or dysesthesia, or palmar-plantar erythrodysesthesia syndrome. There were 7 patients on thyroid hormone replacement who required dose adjustment while on lenvatinib. Treatment was discontinued due to disease progression (4/11), AEs (2/11) and death (1/11), although the latter was attributed to disease progression. The remaining 3 patients continued therapy through their last follow-up.
J Endo Soc. 2022;6(5) © 2022 Endocrine Society