Dr Jones on the Evolving Treatment Landscape in GIST

"The exciting thing here is that [investigational agents such as] NB003 and IDRX-42, will be further evaluated in randomized trials. Hopefully over the next few years, we'll see the approval of even more treatments for patients with metastatic GIST."

Robin Jones, MD, MRCP, a consultant medical oncologist, professor of medical oncology, and head of the Sarcoma Unit at The Royal Marsden NHS Foundation Trust, outlined developments in the evolving treatment landscape for patients with gastrointestinal stromal tumor (GIST), spanning both the adjuvant and metastatic settings.

In the adjuvant setting, Jones highlighted data from the French Sarcoma Group's phase 3 IMADGIST trial (NCT02260505), which randomly assigned patients with high-risk GIST to receive an additional 3 years of imatinib (Gleevec) following completion of the standard 3-year course, compared with patients who discontinued therapy at 3 years. With a median follow-up of 55 months (IQR, 46-59) post randomization, 3 additional years of maintenance imatinib significantly improved disease-free survival, with a HR of 0.40 (95% CI, 0.20-0.69; 

 = .0008) favoring the 6-year arm. However, follow-up remains relatively early, and longer-term data will be needed to fully characterize the benefit, he noted. A complementary phase 3 trial (NCT02413736), led by the Scandinavian Sarcoma Group, has completed accrual and randomly assigned patients with very high-risk GIST to 3 vs 5 years of adjuvant imatinib; results are pending and expected to further inform optimal treatment duration, Jones shared.

In the metastatic setting, Jones emphasized several ongoing and recently completed trials. The phase 3 INSIGHT trial (NCT05734105) is currently enrolling patients with advanced or metastatic GIST and 

 exon 11, 17, or 18 mutations following progression on imatinib. Patients are randomly assigned to receive either ripretinib (Qinlock) or sunitinib (Sutent), with progression-free survival (PFS) as the primary end point. This trial builds on a prior second-line study of ripretinib vs sunitinib, the phase 3 INTRIGUE trial (NCT03673501), which did not meet its primary end point overall but suggested potential benefit in patients with specific 

 mutations based on circulating tumor DNA analyses, Jones explained.

Additionally, the phase 3 PEAK trial (NCT05208047), now closed to recruitment, investigated sunitinib alone vs sunitinib plus the TKI bezuclastinib (CGT9486) in the second-line setting, with PFS as the primary end point. Beyond these, Jones pointed to several promising investigational agents, including NB003 and IDRX-42, which are being explored in early-phase studies and are anticipated to move into randomized trials. These efforts collectively reflect a robust pipeline of therapies aimed at improving outcomes for patients with metastatic GIST, he concluded.

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Robin Jones, MD, MRCP, discusses the treatment armamentarium for patients with gastrointestinal stromal tumors. 

Dr Jones on the Evolving Treatment Landscape in GIST  

Dr Jones on Communication Between Community and Academic Oncologists in Cancer Care

Robin Jones, MD, MRCP, consultant medical oncologist, professor, Medical Oncology, head Sarcoma Unit, The Royal Marsden NHS Foundation Trust, discusses the importance of communication between community and academic oncologists in cancer care, highlighting the impact of multidisciplinary communication.

Effective communication between academic centers and community oncologists holds paramount importance, particularly in the landscape of gastrointestinal stromal tumor (GIST) research, Jones begins. The nature of GIST calls for community oncologists to proactively engage with academic institutions to explore available clinical trials that encompass the spectrum of promising novel agents and treatment approaches emerging in the field of GIST management, he states.

The evolving treatment paradigm presents an opportunity to offer patients innovative treatments, making it essential to initiate discussions about clinical trial participation, especially for those experiencing disease progression, he explains. For instance, 

the phase 3 Peak trial (NCT05208047) is investigating the TKI bezuclastinib

 (CGT9486) in combination with sunitinib (Sutent) vs sunitinib monotherapy in patients with GIST. However, part 2 of this trial is not open to patients who have received therapies beyond first-line imatinib (Gleevec), which highlights the importance of clinical trial awareness when considering treatment sequencing for patients with GIST.

, including the Peak regimen under investigation, may broaden the range of treatment options available to patients, he explains. However, despite the optimistic trajectory of current developments, challenges persist. The prevalence of community oncology practices, although beneficial for widespread health care access, poses logistical challenges for patients seeking trial participation at the academic centers Jones says. Geographical constraints may impede some patients from traveling to specialized centers offering treatments through clinical trials, he notes. Jones goes on to say that, nevertheless, there is a positive outlook regarding recruitment to the Peak trial that draws inspiration from previous successes in enrolling patients in other second-line trials.

Recognizing the historical scarcity of clinical trials in the GIST landscape, the current surge in opportunities signifies a turning point in treatment, he continues. The excitement surrounding ongoing trials and their innovative combination therapy approaches underscores the importance of effective communication regarding these trials, he imparts. Proactively spreading awareness about trials within the medical community and among patients and health care providers can illuminate the potential for a novel second-line treatment for patients with GIST. This multifaceted approach aims to bridge the communication gap between academic and community settings as well as address logistical challenges, ultimately contributing to the successful execution and impact of clinical trials, Jones concludes.

Robin Jones, MD, MRCP, discusses the importance of communication between community and academic oncologists in cancer care.

Robin L. Jones, MD, MRCP

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Dr Jones on the Evolving Treatment Landscape in GIST

Dr Jones on Communication Between Community and Academic Oncologists in Cancer Care