Conference Coverage

Pazopanib extended PFS in patients with carcinoid tumors



– Pazopanib significantly improved progression-free survival (PFS) in patients with progressive carcinoid tumors who were enrolled in a prospective randomized phase 2 trial.*

Median PFS was 11.6 months for patients receiving the small molecule VEGF inhibitor, versus 8.5 months for those receiving placebo (P = .0005), according to results of the Alliance A021202 trial.

This is the first randomized study to show that the vascular endothelial growth factor (VEGF) pathway may be a valid therapeutic target in carcinoid tumors, said investigator Emily K. Bergsland, MD, of the University of California, San Francisco.

However, the potential benefits of pazopanib need to be viewed in light of toxicity risks, including an excess of hypertension, Dr. Bergsland said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

The efficacy results suggest that pazopanib is another promising systemic option for carcinoid tumors, according to William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“Pazopanib does inhibit other targets, including [fibroblast growth factor receptors], which may be of relevance in carcinoid,” Dr. Harris noted in a podium discussion of the A021202 trial results.

Other promising systemic options under investigation include cabozantinib, which he said will be evaluated in phase 3 trials, lenvatinib, and ramucirumab plus a somatostatin analogue.

The CDK4/6 inhibition is of interest and will be pursued in future trials, though unfortunately the role of checkpoint inhibitors is “unclear” in this tumor type, he said.

In the present randomized study of pazopanib, a computer error resulted in slightly more patients being randomized to the pazopanib arm – 89 patients – while 72 were randomized to placebo, according to the investigator.

The rate of grade 3 or greater toxicities was 73.0% for pazopanib, and 7.9% for placebo in the study. Notably, there was a relatively high rate of grade 3 or greater hypertension, at 26.9% versus 4.2% for placebo, though only one case in the pazopanib arm was grade 4, Dr. Bergsland said.

Pazopanib was also associated with more symptoms such as diarrhea, appetite loss, and fatigue, but the overall quality of life was similar between the groups in preliminary analyses, said Dr. Bergsland.

Despite the improved PFS in the pazopanib arm, there was no improvement in overall survival. That’s likely because placebo-treated patients were allowed to cross over to pazopanib upon progression, and two-thirds of them did so, said Dr. Bergsland. The resulting median overall survival was 41.3 months for pazopanib and 42.4 months for placebo.

“Additional work is needed to identify strategies for mitigating toxicity and/or selecting patients most likely to benefit,” Dr. Bergsland said in her presentation.

Toward that end, investigators are looking at strategies including angiome profiling, assessment of tumor growth rate, and textural image analysis, she added.

Dr. Bergsland reported disclosures related to More Health, UpToDate, Advanced Accelerator Applications, Lexicon, Merck, and Novartis.

SOURCE: Bergsland EK, et al. ASCO 2019. Abstract 4005.

Correction, 6/17/19: An earlier version of this article mischaracterized the study type.

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