Genetic analysis helps increase clinical benefits with PARP inhibitors in ovarian cancer and BRCA

Sakth Guntopalli, MD

The use of genetic testing to identify homologous recombination deficiency (HRD) and BRCA Mutations in ovarian cancer could better aid selection of frontline maintenance therapies and improve management of toxicities associated with PARP inhibitors, according to Sakth Guntopalli, MD.

“We go in [a new] The age of the ovarian cancer molecule,” Guntupalli said following OncLive® Institutional perspectives at a cancer webinar on ovarian cancer, which she chaired. We don’t want to give patients drugs that will make them feel bad if they aren’t really effective. Know the signs of toxicity [can elucidate] what [treatment strategy] will work. ”

In an interview with OncLive®Guntupalli highlighted key topics discussed during the meeting, including data supporting PARP inhibitors as standard frontline care treatment, strategies for managing PARP-related toxicities, the importance of HRD testing and BRCA The situation in patients with ovarian cancer.

Guntobali Professor and Director of the Department of Gynecologic Oncology, Karen M. Colorado.

OncLive®: How pivotal studies such as the Phase 3 trials of SOLO-1 (NCT01844986) and PRIMA (NCT02655016) have improved the use of precursor PARP inhibitors in patients with AD BRCAPositive ovarian cancer?

Guntupalli: Those tests have proven essential [the] Need to know [HRD and BRCA mutation status]. The survival curves in those studies are impressive [clearly show] that sick BRCA or human resource development [positivity] Maximum benefit from the use of PARP treatment versus placebo. Solo -1 [in particular] It’s a great study. We see patients [in this study] Who was he BRCA positive years of survival [after receiving] PARP inhibitors. The data is there [to support] The use of PARP treatment in these two groups.

patients who are BRCA negative and negative HRD [also] It appears to benefit from PARP inhibitors. In the PRIMA experience, [patients experienced some form of] Take advantage of PARP treatment whether they are BRCA positive or negative. [These trials contained] risk ratios [between] 0.3 and 0.4 order BRCA-positive [patients] And [between] 0.5 and 0.6 for HRD-positive patients, [which] Great. [Still]showing the greatest benefit in BRCAPositive and human resource development[-positive] Oncology.

In connection with the presentation by your colleague Jill Aldridge, MD, of the University of Colorado Cancer Center, on managing toxicity with PARP inhibitors, what strategies can be used to better address these effects while maximizing clinical benefit?

first in the first place first of all [it is vital to] Talk to patients and find out what bothers them the most. more [common] Toxicity associated with PARP treatment is gastrointestinal toxicity, such as nausea, [which] It generates some other toxicities, such as fatigue and anemia.

[Additionally,] See what the strategies are [patients have already] Try to improve [adverse effects] can [inform the best approach]. Do they split the dose? [in the] morning and afternoon? Do they take it with food? [Are] They took a maximum dose of 300 mg of niraparib [Zejula] every day? [If so]Maybe they should take a dose [level]. [If a patient has] thrombocytopenia, [it is also important to] Make sure they are not taking other medications [may negatively] reacts [with PARP inhibitors. Consideration of these factors] It is the key to managing toxicities.

As mentioned in the presentation by Yevegniya Ioffe, MD, of Loma Linda University Cancer Center, on antibody conjugates in platinum-resistant ovarian cancer, what is the significance of FDA approval of mirvetuximab soravtansine-gynx (Elahere) for this population?

[The accelerated approval] For mirvituximab, soraftansine is very cool, because now we have something to treat patients with folate receptor alpha [expression]; [this is] very Difficult[-to-treat] Patient people. response rate [of mirvetuximab soravtansine] In the third phase of the Soraya experiment [NCT04296890] Conducted by Kathleen Moore, MD, of Stephenson Cancer Center, it was very good [compared with] other response rates [observed with] individual therapy.

Things to keep in mind are the toxicities associated with mirvetuximab soravtansine, [such as] eye toxicity [This] It’s nothing [clinicians] I can ignore, and I [do not] You think someone losing visual acuity is widely accepted. [We] You should be very familiar with these toxicities.

What is the main message you would like to pass on to colleagues regarding the importance of genetic testing in the treatment of ovarian cancer?

Knowledge of human resource development f BRCA [mutation] The condition of the patient with ovarian cancer is the most important [factor for treatment selection] Because this sign [can inform] Use of PARP inhibitors in women with serous ovarian cancer. We need to find out [information] So that we can ensure that patients receive cutting-edge treatment.

it’s a [also] neglected [understand] How and why we lower the dose, as well as things we can do to improve [and monitor] those toxicities. [Lastly,] It is important to [be informed] about new [available treatments] for platinum-resistant disease.

Are there any ongoing studies at the University of Colorado Cancer Center that you’d like to highlight?

we have [several] Things are in the making. they were [currently] Considering the combination of mirvituximab with soraftansine and some other agents is down the road. we [also] PARP toxicity assay [in] immune microenvironment and [trying to understand] What contributes to PARP [inhibitor] resistance in [patients with] BRCA-positive [disease].

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