John Raymond Zalcberg, PhD, MBBS, a professor of Cancer Research in the School of Public Health and Preventative Medicine at Monash University, discusses the rationale for intra-patient dose escalation with ripretinib (Qinlock), as was examined in the phase 3 INVICTUS trial (NCT03353753) in patients with advanced gastrointestinal stromal tumors (GIST). 

In the phase 1 dose-escalation portion of the research, the maximum tolerated dose of ripretinib had not yet been reached, according to Zalcberg, even when given at a daily dose of 400 mg or a twice-daily dose of 200 mg. As such, there was a rationale to increase the dose from a toxicity standpoint the phase 3 trial, Zalcberg notes. However, it was unknown whether the efficacy would be sustained, Zalcberg adds. 

Although TKIs with a variety of targets are sometimes used for patients with GIST who progress on ripretinib, limited approved, active options are available, Zalcberg says. INVICTUS provided patients with an opportunity to benefit from ripretinib, Zalcberg adds. In the clinic, some patients progressed on the daily dose of 150 mg and continued to derive benefit with dose escalation, Zalcberg concludes. 

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John Raymond Zalcberg, PhD, MBBS, discusses the rationale for intra-patient dose escalation with ripretinib, as was examined in the phase 3 INVICTUS trial in patients with advanced gastrointestinal stromal tumors.

Dr. Zalcberg on the Rationale for Dose Escalation With Ripretinib in Advanced GIST 

John Raymond Zalcberg, PhD, MBBS, a professor of Cancer Research in the School of Public Health and Preventative Medicine at Monash University, discusses the efficacy of intra-patient dose escalation with ripretinib (Qinlock) in patients with advanced gastrointestinal stromal tumors (GIST), as demonstrated in an analysis of the phase 3 INVICTUS trial (NCT03353753).

In the analysis, which the strategy was tested following disease progression in patients with GIST, a benefit was observed in patients who were dose escalated, Zalcberg says. After patients progressed on a once daily dose, they had a subsequent benefit with dose escalation that resulted in a median progression-free survival 2 (PFS2)of 3.7 months, Zalcberg notes. This was substantially better than the placebo group, according to Zalcberg.

Although PFS2, defined as the time from the first dose of ripretinib to disease progression or death, was slightly less than the median PFS1, which was 4.6 months and defined as the time from randomization to disease progression, there did appear to be a clear benefit over the placebo group, Zalcberg says.

John Raymond Zalcberg, discusses the efficacy of intra-patient dose escalation with ripretinib in patients with advanced gastrointestinal stromal tumors, as demonstrated in an analysis of the phase 3 INVICTUS trial. 

Dr. Zalcberg on the Efficacy of Intra-Patient Dose Escalation With Ripretinib in Advanced GIST

John Zalcberg, ​PhD, OAM, the Prof & Tony Charlton Chair of Oncology​, head, Cancer Research Program, NHMRC (MRFF) Practitioner Fellow, the School of Public Health and Preventive Medicine, Monash University, discusses the approval of avapritinib (Ayvak​it) in gastrointestinal stromal tumor (GIST).

 for ​the treatment of adult ​patients with unresectable or metastatic GIST who harbor a 

​Findings from the phase 1 NAVIGATOR trial, which led to the regulatory decision, demonstrated a high overall response rate of 84% in patients who received avapritinib and harbored a 

Additionally, the ORR was 89% in the population of patients with 

 D842V mutations, which included an 8% complete response rate and an 82% partial response rate.

Avapritinib now has a ​significant role in the management of patients with unresectable or metastatic GIST​, Zalcberg concludes.

John Zalcberg, ​PhD, OAM, discusses the approval of avapritinib in gastrointestinal stromal tumor.

Dr. Zalcberg on the Approval of Avapritinib in GIST

John Zalcberg, ​PhD, OAM, the Prof & Tony Charlton Chair of Oncology​, head, Cancer Research Program, NHMRC (MRFF) Practitioner Fellow, the School of Public Health and Preventive Medicine, Monash University, discusses the role of ripretinib (Qinlock) in advanced gastrointestinal stromal tumor​ (GIST).

Ripretinib, a switch kinase inhibitor ​that targets KIT and PDGFRα, is one of the latest additions to the ​advanced GIST armamentarium, says Zalcberg.

The agent was evaluated in the randomized ​phase 3 

that showed ripretinib could overcome resistant phenotypes​, Zalcberg explains.

Based on ​findings from this trial, ripretinib received regulatory approval ​from the FDA on May 15, 2020 for the ​fourth-line treatment of adult patients with advanced GIST who have received 3 or more prior kinase inhibitors, including imatinib (Gleevec).

Ripretinib offers an additional option beyond imatinib,​ sunitinib (Sutent), and ​regorafenib (Stivarga) for the treatment of patients with advanced GIST, Zalcberg explains.

Due to the encouraging results that have been observed with this agent in the United States, ripretinib may receive ​global approval​s in the future, Zalcberg concludes.

John Zalcberg, ​PhD, OAM, discusses the role of Gastrointestinal Cancer in advanced gastrointestinal stromal tumor​. 

Dr. Zalcberg on the Role of Ripretinib in Advanced GIST

John Zalcberg, ​PhD, OAM, the Prof & Tony Charlton Chair of Oncology​, head, Cancer Research Program, NHMRC (MRFF) Practitioner Fellow, the School of Public Health and Preventive Medicine, Monash University, discusses the management of patients with gastrointestinal stromal tumor​ (GIST).

​Multiple options are available to treat patients with GIST, Zalcberg says. Although many patients will progress through treatment, agents such as imatinib (Gleevec), ​sunitinib (Sutent), and ​regorafenib (Stivarga) can be given with manageable toxicity. Moreover, ripretinib (Qinlock) is approved as a fourth-line therapy for these patients.

GIST is the most common subtype of sarcoma that presents in the gastrointestinal tract. Research in this space continues to unfold, leading to improved outcomes for patients, Zalcberg concludes.

John Zalcberg, ​PhD, OAM, discusses the management of patients with gastrointestinal stromal tumor​. 

Dr. Zalcberg on the Management of Patients With GIST

John Zalcberg, ​PhD, OAM, the Prof & Tony Charlton Chair of Oncology​, head, Cancer Research Program, NHMRC (MRFF) Practitioner Fellow, the School of Public Health and Preventive Medicine, Monash University, discusses updated results from the phase 3 INVICTUS trial in advanced gastrointestinal stromal tumor (GIST).

In the phase 3 INVICTUS study, patients with advanced GIST who received 4 or more prior lines of therapy were randomized 2:1 to receive 150 mg of ripretinib (Qinlock) or placebo. The primary end point of the study was progression-free survival (PFS).

showed ​that PFS was 6.3 month​s with ripretinib versus 1 month with placebo, says Zalcberg. The hazard ratio was 0.16; however, a formal 

Regarding safety, the adverse effects (AEs) ​observed with ripretinib were similar to other TKIs. Though, there was a higher incidence of alopecia in the ripretinib arm. Overall, the agent was well tolerated, explains Zalcberg.

Notably, throughout the duration of treatment, quality of life was either maintained or improved with ripretinib ​compared with placebo, Zalcberg concludes.

John Zalcberg, ​PhD, OAM, discusses updated results from the phase 3 INVICTUS trial in advanced gastrointestinal stromal tumor.

John Zalcberg, PhD, OAM

Articles

Dr. Zalcberg on the Rationale for Dose Escalation With Ripretinib in Advanced GIST

Dr. Zalcberg on the Efficacy of Intra-Patient Dose Escalation With Ripretinib in Advanced GIST

Dr. Zalcberg on the Approval of Avapritinib in GIST

Dr. Zalcberg on the Role of Ripretinib in Advanced GIST

Dr. Zalcberg on the Management of Patients With GIST

Dr. Zalcberg on Updated Results from the Phase 3 INVICTUS Study in Advanced GIST