1) Welcome to the next installment of our #accredited serialized #tweetorials from @onc_ce, your new (& only) home for the latest education from #experts on #cancer care. #Physicians #nurses #pharmacists #PAs and #NPs can all earn 0.5h CE/#CME by following this thread!
2) This one comes from @ASCO #GI22, which just wrapped up last month. Our expert author is Dr. Dale Shepard (@ShepardDale) from @ClevelandClinic in Cleveland, OH and the topics are #GIST & updates on some trials for patients with advanced #MSS #colorectalcancer.
3) This program on @onc_ce is supported by an educational grant from Bayer and content is intended for #healthcare providers. Faculty disclosures are listed at http://www.oncologytweetorials-ce.com/disclosures/. Earn credit from prior programs posted on http://www.oncologytweetorials-ce.com!
5) So let's start with a quick knowledge ✔️. Which of the following therapies is approved for patients with metastatic #GIST who have received #imatinib and at least two other tyrosine kinase inhibitors?— @onc_ce (@onc_ce) February 9, 2022
6) Here’s more about a trial for pts w/metastatic GIST. Ripretinib is a broad spectrum switch control kinase inhibitor of KIT & PDGFR w/better in vitro activity than sunitinib for imatinib-resistant secondary KIT mutations & a median PFS of 10.7 in second-line in a Ph I study.
7) The INTRIGUE trial was a phase III that tested the hypothesis that by broadly treating KIT mutations, ripretinib would be superior to sunitinib as second line therapy for patients with advanced GIST.
8) The results from the #INTRIGUE trial were presented as the Plenary Session at @ASCO #GI22 by Dr. Michael Heinrich from Oregon Health & Science University @OHSUNews.
9) As shown here, in the INTRIGUE trial patients with GIST with progression on or intolerance to imatinib to receive either ripretinib or sunitinib with PFS by independent radiology review as the primary endpoint.
10) This was an international study that was very evenly matched between the 2 groups for location, ECOG status, intolerance to imatinib, & importantly the mutation status, which is now a very important part of the management of advanced GIST.
11) It is notable that with accrual of 453 patients, this was a relatively large trial for a study enrolling patients with a rare tumor.
12) Was ripretinib better than sunitinib for the primary endpoint of PFS as determined by independent radiology review? No…not in patients with the most common KIT exon 11 mutation (8.3 months vs 7 months) or in all patients (8 months vs. 8.3 months)
13) Patients were stratified by mutation subtype on enrollment. A proposed benefit to earlier use of ripretinib was activity across many mutation subtypes. Was the PFS longer in any mutation subtype treated with ripretinib?
14) No…but patients with a KIT exon 9 mutation benefited more from sunitinib.
15) So, no differences in PFS, but what about ORR, one of the key secondary endpoints? Yes and no. Ripretinib was associated with an increased ORR in patients with a KIT exon 11 mutation, but not in all patients.
16) How about ease of use for each therapy? While 38.1% of patients receiving ripretinib had a dose modification, 63.3% of patients receiving sunitinib had a modification of the dose.
17) In all fairness, sunitinib was given with the 4 weeks on and 2 weeks off schedule in this trial. Many patients with GIST may benefit from the lower dose continuous dosing schedule with fewer side effects and constant suppression of KIT.
18) With the dose schedule given in the INTRIGUE study, ripretinib was better tolerated than sunitinb with 26.5% of patients having grade 3/4 treatment related toxicity compared with 55.2% for patients receiving sunitinib.
19) The most common Grade 3 or 4 treatment related adverse event for both ripretinib and sunitinib was hypertension.
20) While Dr. Heinrich reiterated the comparable PFS between ripretinib and sunitinib and the more favorable safety, ripretinib did not meet the primary endpoint of a superior PFS over sunitinib, & INTRIGUE was a negative study.
21) In the discussion of the INTRIGUE trial, Dr. George Demetri @DrSarcoma, Director Sarcoma Center at Dana-Farber Cancer Institute @DanaFarber, highlighted that the disease control rate was similar for both drugs . . .
22) . . . and there were fewer toxicities with ripretinib which is good for patients….but since toxicity wasn’t the primary endpoint the trial was an “intriguing failure”. See the @OncoAlert video recap at
23) Let’s switch gears. Please return TOMORROW and we’ll discuss @ASCO #GI22 data on patients with #MSSCRC in trials of immune checkpoint inhibitors alone, which has led to trials of these agents in combination with other therapies. Shout outs to @aakonc @SKamath_MD @pashtoonkasi
24) Welcome back! @ShepardDale is leading us through highlights of data from @ASCO #GI22 on #GIST & advanced #MSS #colorectalcancer. You’re earning 0.5h CE/#CME by following this thread! Hello to @DocCatenacci @ErikaHamilton9 @DrHBurstein @NarjustDumaMD @OncBrothers @PamelaKunzMD
25) In patients with #MSSCRC there has historically been poor response to #immune #checkpoint inhibitors alone. This has led to trials of these agents in combination with other therapies.
26) Dr. Afsaneh Barzi @Dr_AfsanehBarzi from City of Hope @cityofhope (and @ClevelandClinic alumna) presented results of a phase I/II trial with patients with advanced MSS CRC treated with #pembrolizumab in combination with #regorafenib.
27) This was a straightforward study design. A phase I portion with increasing doses of regorafenib with pembrolizumab and a phase II part with pembrolizumab in combination with regorafenib at the recommended phase II dose in patients who failed chemotherapy.
28) The recommended phase II dose of regorafenib was 80 mg on days 1-14 every 21 days. The most common grade 3 toxicities were rash (20%), hand-foot syndrome (7%) and #hypertension (7%)
29) Did it work? Unfortunately, no. While 49% of patients had stable disease, there were no objective responses and the median PFS of 2 months failed to meet the primary endpoint.
30) Time for another combination? Dr. Tyler Friedrich at University of Colorado presented preliminary data from a phase II trial with a combination of pembrolizumab, #binimetinib and #bevacizumab in patients with treatment-refractory MSS #colorectalcancer.
31) This combination showed better activity than the combination of pembro and regorafenib. The median PFS was 5.8 months, with an objective response rate of 13%. 62% of patients had stable disease. See https://www.targetedonc.com/view/roundtable-discussion-kundranda-and-participants-review-first-line-and-later-line-therapies-in-crc from @TargetedOnc
32) Most common adverse events Grade 3 or greater included elevated transaminases (15%), diarrhea (11%), acneiform rash (9%), #hypertension (9%) and #anemia (9%).
33) This preliminary data suggests that there may be a role for immunotherapy combinations in patients with MSS CRC. It is likely that there will be many other combinations in the future.
34) A key to successful treatment of patients with MSS CRC with immunotherapy combinations may depend on use of biomarkers to select patients or monitor therapy.
35) At @ASCO #GI22, Dr. Marwan Fakih @mgfakih from City of Hope http://www.coh.org presented some exploratory biomarker data from a Ph 2 trial that has been reported previously from patients with #chemotherapy-resistant MSS CRC treated with #regorafenib & #nivolumab.
36) What was measured? Immune-related biomarkers by immunohistochemistry, gene expression profiling by RNA sequencing, circulating tumor DNA, & soluble biomarkers. Samples were collected at baseline and during cycle 2.
37) Were there any positive findings? There was a trend for anti-tumor activity with higher baseline expression of biomarkers for immune sensitivity. Elevated cytotoxic T cell density during cycle 2 did not correlate with anti-tumor activity.
38) Serum markers related to angiogenesis were associated with an inferior anti-tumor response.
39) While these are hypothesis-generating findings, they point to the possibility that the proper therapies can be chosen for each patient or the efficacy of therapies can be estimated early in the course of treatment.
40) And that’s it! Now go and claim your FREE CE/#CME at https://oncologytweetorials-ce.com/GIST_regorafenib and FOLLOW US for more #accredited #tweetorials for #physicians #pharmacists #nurses #physicianassociate #nursepractitioner. Bravo to @ASCO #GI22 for keeping the show going!
Originally tweeted by @onc_ce (@onc_ce) on February 9, 2022.