Key takeaways:
- The addition of anlotinib to straightforward of look after newly identified glioblastoma considerably improved PFS in a randomized phased 2 trial.
- Nevertheless, OS didn’t differ between anlotinib and placebo arms.
CHICAGO — Including anlotinib to straightforward temozolomide-based chemoradiotherapy considerably prolonged PFS for newly identified glioblastoma in a randomized part 2 trial, in keeping with findings offered at ASCO Annual Assembly.
Anlotinib (Advenchen Laboratories, Jiangsu Chia-Tai Tianqing Pharmaceutical) plus radiation remedy and concomitant temozolomide (STUPP routine) diminished the danger for development 31% in contrast with STUPP alone.
Knowledge derived from Chen Y, et al. Summary LBA2000. Offered at: ASCO Annual Assembly; Might 30-June 3, 2024; Chicago.
Nevertheless, questions stay concerning the routine’s influence on OS.
Research presenter Yuanyuan Chen, MD, of Solar Yat-sen College Most cancers Middle, described the remedy as a “promising therapeutic technique.”
“The oral administration of anlotinib presents logistical benefits that will improve affected person adherence and remedy accessibility, doubtlessly enhancing general high quality of life,” she mentioned.
New technique wanted
Sufferers with newly identified glioblastoma who obtain STUPP, which turned normal of care in 2005, have a 2-year OS of 26.5% and 5-year OS of 9.8%, in keeping with research background.
“The prognosis stays poor,” Chen mentioned.
A main function of glioblastoma is angiogenesis. Anlotinib is an anti-angiogenic drug that targets VEGFR1/2/3, c-Equipment, PDGFR alpha/beta and FGFR1/2/3.
Chen and colleagues investigated whether or not anlotinib might enhance prognosis on this affected person inhabitants.
Researchers randomly assigned 153 adults with newly identified glioblastoma and an ECOG efficiency standing of 0 to 2 to obtain STUPP plus 10 mg anlotinib (days 1-14 per 21-day cycle) or placebo.
Contributors had six cycles of STUPP and eight cycles of anlotinib or placebo. They continued to obtain anlotinib or placebo till illness development or unacceptable toxicity.
The anlotinib arm had 77 sufferers (median age, 55.4 years; 64.9% males; median follow-up, 27.53 months) and the placebo had 76 (median age, 55.1 years; 56.6% males; median follow-up, 31.05 months).
Impartial assessment committee (IRC)-assessed PFS served as the first endpoint. OS, investigator-assessed PFS, goal response charge, illness management charge and security served as secondary endpoints.
Does anlotinib enhance survival?
Sufferers who obtained anlotinib had considerably longer IRC PFS in contrast with those that obtained placebo (median, 9.89 months vs. 5.85 months; HR = 0.59; 95% CI, 0.42-0.85) and investigator-assessed PFS (median, 12.45 months vs. 8.08 months; HR = 0.57; 95% CI, 0.39-0.84).
Additionally they had considerably improved IRC ORR (16.88% vs. 5.26%; P = .022) and IRC illness management charge (50.65% vs. 32.89%; P = .026).
General, the anlotinib arm had related OS because the placebo arm (17.02 months vs. 17.18 months), however sufferers with MGMT promoter methylation standing did expertise OS profit (HR = 0.31; 95% CI, 0.12-0.79).
“Submit-progression remedy could have confounded OS,” Chen mentioned.
Sufferers who obtained anlotinib had a decrease charge of treatment-emergent hostile occasions (93.5% vs. 96.1%), however the next charge of treatment-related hostile occasions (92.2% vs. 85.5%), critical hostile occasions (35% vs. 25%), treatment-related critical occasions (16.8% vs. 9.2%) and grade 3 or worse treatment-related critical occasions (11.7% vs. 6.6%).
The most typical grade 3 or worse hostile occasions included thrombocytopenia (anlotinib, 7.8% vs. placebo, 1.3%), neutropenia (6.5% vs. 3.9%), lymphopenia (6.5% vs. 7.9%), leukopenia (6.5% vs. 2.6%) and hypertension (5.2% vs. 0%).
Chen acknowledged research limitations, together with the small pattern measurement, enrollment solely from facilities in China and potential influence of the COVID-19 pandemic.
Discussant Eudocia Q. Lee, MD, MPH, director of scientific analysis for neuro-oncology at Dana-Farber Most cancers Institute and affiliate professor of neurology at Harvard Medical College, emphasised the dearth of OS profit and the way PFS “most likely isn’t” an excellent surrogate endpoint for anti-angiogenic medication, throughout her presentation.
She highlighted a number of research of different medication within the class, together with bevacizumab (Avastin, Genentech), cediranib and regorafenib, which additionally demonstrated PFS enchancment however not OS profit.
“The PFS prolongation is possibly a byproduct of our lack of ability to precisely decide response charges within the setting of angiogenesis inhibitors,” Lee advised Healio. “They type of alter the blood mind barrier, so it could make visualization of the tumor harder. That’s what has at all times been speculated with bevacizumab, cediranib and different anti-angiogenic brokers as to why we don’t see an general survival profit from these explicit medication.”
Anti-angiogenic medication can have advantages. Bevacizumab is FDA permitted and has anti-edema results, Lee mentioned.
“There may be some scientific profit that comes from these medication,” she added. “It’s to not say they’re ineffective. Do they really influence survival is a distinct query.”
She famous the OS survival curves for sufferers with MGMT promoter methylation standing, but additionally the small pattern measurement and want for extra mature information.
“It might nonetheless be significant,” Lee mentioned. “Why would we see a profit simply within the methylated group however not the unmethylated group? It’s not just like the drug has some goal that you simply see in greater charges in sufferers [with MGMT promoter methylation status] that you’d say that’s why it impacts [those] sufferers in another way.”
She added: “On the DNA degree, by way of copy quantity variation and particular gene mutations, we don’t see variations between methylated and unmethylated amongst newly identified sufferers. Perhaps we don’t know what’s taking place on the RNA degree. Epigenetically is one thing taking place and possibly that explains the variations in profit between the 2 teams? A whole lot of unknowns.”
Sources/Disclosures
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Chen Y, et al. Summary LBA2000. Offered at: ASCO Annual Assembly; Might 30-June 3, 2024; Chicago.
Disclosures:
Chia Tai Tianqing Pharmaceutical Group Co. Ltd. sponsored the research. The authors report no related monetary disclosures. Lee reviews consulting or advisory roles with World Coalition for Adaptive Analysis and royalties from Wolters Kluwer for UpToDate.
