Part 2: Using PARP Inhibitors Beyond Recommended Duration in Ovarian Cancer

Adam C. ElNaggar, MD (Moderator)

Gynecologic Oncologist

Oncology Medical Director

Natera

Memphis, TN

DISCUSSION QUESTION:

• Would you continue treating a patient who has received PARP inhibitors for the full duration of maintenance therapy?

MICHAEL HEMPHILL, MD: I haven’t gotten to the 2-year mark for olaparib [Lynparza] or the 3-year mark for niraparib [Zejula],¹ but if I got to that, I’d be very hard-pressed to stop if they’re doing it well. I think I’d almost treat it like imatinib [Gleevac] in a gastrointestinal stromal tumor scenario.^2,3

ADAM C. ELNAGGAR, MD: Just keep running it?

HEMPHILL: Yes, I think so.

ELNAGGAR: Yes. That’s tough, and that conversation can be tough, too, In the front line, sometimes patients are ready to come off of it, but in the recurrent setting where their cancer antigen 125 is normal; they don’t have any symptoms; their CT scan’s negative; it’s time to come off of it. And [they say], “Look, you told me recurrence is incurable, and here I am, I want to stay on it.” Has anybody else run into that dilemma as to whether to stop at 2 or 3 years?

HASSAN GHAZAL, MD: I agree with what’s been said. In the first-line setting, it’s easier to tell the patients because of the cumulative toxicity, and in the first line where you think the [Kaplan-Meier] curve is more flat after you stop the treatment, at least from what we saw in SOLO-1 [NCT01844986] and others.^4-6 It’s certainly weighing emerging toxicity versus benefit. I would feel more comfortable stopping in the first line, but as you said, in the recurrent setting it’s a different discussion. But you always weigh positives and negatives.

ELNAGGAR: I’m assuming all of you have experience with PD-L1 inhibitors and [similar regimens]. Those always recommend stopping at 18 months. Is this a hard-and-fast rule for you on immunotherapies, or do you generally keep those going? I know at our center, [opinions] are split. Some physicians will just keep on going because they’ll say there’s no evidence to stop, but others hold to that rule.

ZUHAIR GHANEM, MD: I feel this should depend on the bulk of the disease, and the degree of the metastatic disease. If you have a patient with bulky disease and more extensive stage IV metastatic disease as compared with more limited stage III disease, both of them will need the maintenance therapy because both of them are treated with up-front chemotherapy, but I would be more hesitant to stop treatment for the more bulky disease or the more widely-spread metastatic disease, than the patient with more limited disease.

ELNAGGAR: You’re talking about a patient that still has measurable disease, right?

GHANEM: Not necessarily. Even if the patient has no measurable disease, and the first scan showed more extensive disease then limited intra-abdominal disease that was completely removed by surgery, I feel the bulk of the disease, the patient age, and the patient tolerance really dictate if the 2-year duration is where to stop. It’s the same with lung cancer, too. The 2 years with immunotherapy is where most of the oncologists will probably stop. But, if you have a patient with a more widely spread disease up-front, and they responded so well to immunotherapy, I am usually hesitant to stop the treatment because I know how bad the disease was to start with. And, if it comes back, it won’t be easy to put it back to rest. That’s just my feeling.

VENU MADHAV KONALA, MD: For most patients who had a complete response, I generally stop after 2 years, but if they have a partial response and if they have 1 or 2 lesions left, I generally biopsy those lesions to see if they have active disease. If they have active disease, we go for other options like stereotactic radiation to get them off treatment, because they have oligometastatic disease with only 2 sites of disease.

ELNAGGAR: Yes, so you go after an oligo-metastasis at that point in time.

KONALA: Yes, at that time, if it’s still persistent. Based on the patient, we do different things. But generally, most clinical trials they stop the immunotherapy at 2 years in metastatic disease.

But obviously, as Dr Ghanem mentioned, if it is a widespread metastatic disease, most of us are uncomfortable [stopping treatment]. I had a patient with melanoma who went on [immunotherapy] for 5 years, and he doesn’t want to stop it. He’s not free of disease. It’s a discussion between you and the patient.

If it comes back, we can restart it, but some patients are very uncomfortable stopping it at that point, because they are doing so well and they don’t have any adverse events. They’re just coming once every 6 weeks, since pembrolizumab [Keytruda] is approved for every 6 weeks now, so some of them are very reluctant to stop if they have stage IV disease.⁷

ELNAGGAR: Yes, their initial tumor burden definitely plays into that in terms of the gestalt of [factors for] whether to stop or not.

_References:

_{1. NCCN. Clinical Practice Guidelines in Oncology. Ovarian cancer/fallopian tube cancer/primary peritoneal cancer, version 1.2022. Accessed February 24, 2022. https://bit.ly/3BN2gC6}

_{2. Lopes LF, Bacchi CE. Imatinib treatment for gastrointestinal stromal tumour (GIST). J Cell Mol Med. 2010;14(1-2):42-50. doi:10.1111/j.1582-4934.2009.00983.x}

_{3. Balachandran VP, DeMatteo RP. Gastrointestinal stromal tumors: who should get imatinib and for how long?. Adv Surg. 2014;48(1):165-183. doi:10.1016/j.yasu.2014.05.014}

_{4. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858}

_{5. González-Martín A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962}

_{6. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361}

_{7. Pembrolizumab (Keytruda). Prescribing information. Merck & Co., Inc.; 2021. Accessed February 24, 2022. https://bit.ly/3hevcJY}