The results from the FIRSTMAPPP study, presented at the ESMO Congress 2021, provide compelling evidence for the use of sunitinib in patients with malignant progressive pheochromocytoma and paraganglioma (MPP), a rare cancer. This first randomized, double-blind trial of sunitinib in MPP demonstrated that the 12-month progression-free survival (PFS) rate in patients receiving sunitinib was 35.9%, significantly higher than the 18.9% seen in the placebo group. The study met its prespecified target to increase PFS from 20% to 40%. The study enrolled 78 patients over 8 years, 60% of whom had received prior therapy.
Prof. Juan Valle from the University of Manchester emphasized the importance of these results, noting that none of the existing treatments for advanced MPP are supported by randomized clinical trial evidence. He highlighted that sunitinib's 12-month PFS rate was nearly double that of placebo, and that its good tolerability could provide a much-needed alternative to the older, more toxic therapies currently used for MPP, such as cyclophosphamide, vincristine, and dacarbazine.
Additionally, findings from the phase III SPINET trial suggest that somatostatin analogues (SSAs), like lanreotide, may be beneficial in treating bronchopulmonary (BP) NETs, expanding their use beyond gastrointestinal (GI) NETs. In this study, 77 patients with advanced somatostatin receptor-positive BP NETs were treated with lanreotide autogel, showing a median PFS of 16.6 months compared to 13.6 months with placebo. The benefit was more pronounced in patients with typical carcinoid (TC) tumors (PFS of 21.9 months vs. 13.9 months), compared to those with atypical carcinoid (AC) tumors (PFS of 13.8 months vs. 11.0 months). This finding supports the notion that SSAs are particularly useful in well-differentiated, low-grade tumors.
The AXINET trial also provided valuable insights into the use of VEGFR inhibitors in treating non-pancreatic NETs. This phase II/III trial compared octreotide plus the selective VEGFR inhibitor axitinib with octreotide plus placebo in advanced progressive grade 1–2 extra-pancreatic NETs. The updated results showed a significant PFS advantage for the axitinib group, with a median PFS of 16.6 months compared to 9.9 months for placebo (hazard ratio 0.71; p=0.02). This data suggests that VEGFR inhibition, typically limited to pancreatic NETs, may also be effective in non-pancreatic NETs, including lung NETs.
Prof. Valle summarized that these three trials highlight the comparable efficacy of different treatment modalities—tyrosine kinase inhibitors (TKIs), SSAs, and VEGFR inhibitors—across various NET subgroups. The extension of SSA treatment to BP NETs aligns with current practices in treating GI and pancreatic NETs, and the AXINET trial suggests that VEGFR inhibitors can be used beyond pancreatic NETs. These findings underscore the importance of expert centers and collaboration in advancing treatment options for patients with rare NETs. They also emphasize the potential of future trials to expand these therapies to even broader patient populations.