CFAH VHIO at ESMO 2021: reporting treatment advances against neuroendocrine and endocrine tumors – VHIO – Vall d'Hebron Institute of Oncology

VHIO at ESMO 2021: reporting treatment advances against neuroendocrine and endocrine tumors

Barcelona, September 21, 2021. Featuring among our pre-selection pick of VHIO (co) led research (1) that has subsequently headlined during this week’s virtual 2021 annual Congress of the European Society for Medical Oncology (ESMO), 18-21 September, the following contributions have reported treatment advances against neuroendocrine tumors (NETs) and endocrine cancers:

COSMIC-311: delivering a new standard of care for patients with thyroid cancer

Presented during a Mini Oral Session, Jaume Capdevila, a Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal & Endocrine Tumors Group (Director, Josep Tabernero, PI: Teresa Macarulla), revealed the final results of the double-blind phase III COSMIC-311 study which evaluated the efficacy and safety of targeted therapy, cabozantinib, versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) who had progressed during/after prior VEGFR-targeted therapy for whom there is no standard of care.

Reported earlier this year, the interim results of this pivotal trial were presented at the American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, 04 – 08 June. Achieving the primary endpoint of progression-free survival (PFS), in all randomized patients including those who had previously received lenvatinib, cabozantinib showed clinical and statistical improvements in PFS over placebo, with no unexpected toxicities.

At final analysis, a total of 258 patients with previously treated RAIR-DTC whose disease had progressed after prior VEGFR-targeted therapy, participated, with a longer median follow-up of more than ten months. These patients were stratified based on prior treatment with VEGFR inhibitor, lenvatinib, and age (older or younger than 65 years), both of which are well-defined prognostic factors.

“Our results confirm the superior efficacy and manageable safety profile of cabozantinib as reported in the interim analysis, with improved progression-free survival, irrespective of prior VEGFR-targeted therapy. Cabozantinib has achieved a spectacular 80% reduction in the risk of disease progression in these patients,” said Jaume Capdevila, head of the Neuroendocrine Tumors Unit at Vall d’Hebron.

He added, “Based on these results, the US Food and Drug Administration has just granted approval of this therapy as a new standard of care for this patient population. This represents new hope for these patients who are in particular need of new treatment options.”

We expect that the European Medicines Agency will soon follow suit by approving this treatment for patients with radioactive iodine–refractory differentiated thyroid cancer who have progressed following prior VEGFR-targeted therapy,” concluded Jaume Capdevila.

Immunotherapy for neuroendocrine tumors: new horizons?

To-date immune-based therapies have not led to improved outcomes for patients with neuroendocrine tumors. Results of several studies presented at ESMO21, combining immunotherapy with other therapies including chemotherapy,  are now showing promise in more effectively treating several tumor types, including neuroendocrine cancers. Among the reported studies, are those that have been designed and conducted by investigators of the Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE), whose President is VHIO’s Jaume Capdevila.

Led by GETNE researchers, Jorge Hernando, a Medical Oncologist and Clinical Investigator of VHIO’s Gastrointestinal and Endocrine Tumors Group, presented latest data from the prospective open-label phase II DUNE trial during a Mini Oral session (2). This multi-cohort study, directed by Jaume Capdevila, was designed to assess the combination of anti-PD-L1 monoclonal antibodies durvalumab plus tremelimumab and the activity of systemic therapies after progression on immune checkpoint blockade in 123 heavily pretreated patients with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic or lung origins.

Results showed that progression-free survival, response rates, and overall survival was higher in this patient population, particularly in patients with high grade tumors, than those expected for this subgroup,” observed Jorge Hernando, first author of this study.

 “These immune-based therapies may have an effect on patients that improves the efficacy of subsequent treatments. Our findings open a new potential study concept of sequential therapies, including immunotherapy, for the treatment of neuroendocrine tumors,” concluded Jorge Hernando.

Preliminary data from another GETNE-led study, the phase II NICE­-NEC trial, were presented by lead author Maria Carmen Riesco-Martínez during a Proffered Paper Session (3).  NICE-NEC was designed to explore the efficacy of combining an anti-PD-L1 monoclonal antibody, nivolumab, with chemotherapy as first-line treatment of unresectable, locally advanced or metastatic neuroendocrine cancers of the gastroenteropancreatic tract or unknown origin.

“This is the very first study to evaluate a combination of immunotherapy with chemotherapy in this particular tumor type, representing uncharted territory up until now,” said Jaume Capdevila, who is also an investigator of this NICE-NEC phase II.

Initial findings show promising activity, reporting a disease control rate of 84%, and a 50% overall response rate. The researchers also observed a median progression-free survival rate of 5.7 months, and at 6 months, 39% of patients continued to be disease progression-free.

Notably, the addition of nivolumab did not lead to an increase in the toxicity of standard chemotherapy, but we are still waiting on final survival data, and translational studies underway,” concluded Jaume Capdevila.

VEGFR-1,2,3 inhibition in combination

Jaume Capdevila is also a co-author of the randomized, double-blind AXINET phase II/III study designed to assess the efficacy of a potent and selective VEGFR-1,2,3 inhibitor, axitinib, in combination with octreotide LAR versus placebo and octreotide LAR in patients with advanced G1-2 extra-pancreatic neuroendocrine tumors (NETs).

Earlier findings from this study were reported by lead author Rocio Garcia-Carbonero, Hospital Universitario 12 de Octubre, Madrid (Spain), at the virtual ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Results showed that while the study failed to demonstrate a significant progression-free survival benefit per investigator assessment, axitinib in combination with octreotide LAR demonstrated activity and had a tolerable safety profile in this patient population.

Upon subsequent central blinded radiological progression-free survival assessment studies, Rocio Garcia-Carbonero presented the latest, positive results of this study during a Proffered Paper Session at ESMO21.

Considering that angiogenesis plays an important role in the development and progression of neuroendocrine tumors, the AXINET investigators sought to assess the efficacy of axitinib, which has already shown clinical activity in other vascular-dependent solid tumors, for the treatment of NETs.

A total of 1256 patients were randomized to two arms, one receiving axitinib in combination with octreotide LAR and the other, receiving placebo plus octeotride LAR. “In the group of well-differentiated gastrointestinal and pulmonary neuroendocrine tumors, a better response rate and improved progression-free survival were achieved,” noted Jaume Capdevila.

Data showed that the group receiving the combined treatment achieved a median of 16.6 months of progression-free survival versus 9.9 months in the control group. Axitinib also significantly improved objective response rate in combination with octreotide LAR compared with placebo; 13.2% versus 3.2%, respectively.

“We are optimistic about these positive results. Considering that effective therapeutic options for this tumor type are limited, our findings warrant further studies,” he concluded.

References:

  1. VHIO News: https://www.vhio.net/esmos-2021-virtual-congress-16-21-september-a-pick-of-vhio-research-highlights/.
  2. LBA67 – Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Updated results from the phase III COSMIC-311 trial and prespecified subgroup analyses by prior therapy. These data were presented by Jaume Capdevila during the Mini Oral Session – NETs and endocrine tumours, Monday 20 September 2021, 17:30 to 18:20h (CEST), Channel 5.
  3. 1099MO – Durvalumab plus tremelimumab influence on response to subsequent treatments in patients with neuroendocrine neoplasms (NENs) of gastroenteropancreatic and lung origins: Results from the phase II DUNE trial (GETNE 1601). Results of this study were presented by Jorge Hernando during the Mini Oral Session – NETs and endocrine tumours, Monday 20 September 2021, 17:30 to 18:20h (CEST) on Channel 5.
  4. 1098O – Nivolumab plus platinum-doublet chemotherapy as first-line therapy in unresectable, locally advanced or metastatic G3 neuroendocrine Neoplasms (NENs) of the gastroenteropancreatic (GEP) tract or unknown (UK) origin: Preliminary results from the phase II NICE-NEC trial (GETNE T1913). Findings from this phase II were presented by Maria Carmen Riesco-Martinez during the Proffered Paper Session – NETs and endocrine tumours, Tuesday 21 September 2021, 13:30 to 14:50h (CEST) on Channel 3.
  5. 1097O – The AXINET trial (GETNE1107): Axitinib plus octreotide LAR improves PFS by blinded central radiological assessment vs placebo plus octreotide LAR in G1-2 extrapancreatic NETs. Data was presented by Rocio Garcia-Carbonero during the Proferred Paper Session – NETs and endoncrine tumours, Tuesday 21 September 2021, 14:20 -14:50h (CEST) on Channel 3.
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