Kristie L. Kahl

Lynparza (olaparib) significantly prolonged overall survival (OS) compared with Xtandi (enzalutamide) or Zytiga (abiraterone) plus prednisone in men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in BRCA1, BRCA2 or ATM, and whose disease had progressed during previous treatment with a next-generation hormonal agent.

In particular, the risk of death was 31% lower with Lynparza than with control therapy despite substantial crossover from control therapy to Lynparza.

Updated findings from the randomized, open-label phase 3 PROfound trial were presented at the 2020 European Society for Medical Oncology Virtual Congress and were simultaneously published in 

“Exploratory analysis suggests that patients with BRCA mutations achieve the most benefit and additional studies may be required to further delineate genomic indicators of PARP response, particularly for those with less common gene alterations,” Dr. Joaquin Mateo, of Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona, Spain, said during a virtual presentation of the updated OS findings.

“PROfound is the first randomized trial to prospectively demonstrate overall survival improvement in a molecularly-defined subset of prostate cancer, supporting implementation of genomic testing in daily clinical practice,” he added.

Median OS was superior with Lynparza compared with control therapy in group A (19.1 months versus 14.7 months) and group B (14.1 months versus 11.5 months).

The crossover-adjusted analysis included 86 of 131 patients (66%) in the control group who had crossed over to receive Lynparza, including 56 (67%) patients in group A. Patients were eligible for crossover if they had radiographic disease progression, no other subsequent anticancer therapy, any toxicities from prior therapy less than or equal to grade 1, and agreed to continue with the study visit schedule.

Median duration of treatment with Lynparza in patients who crossed over was 4.8 months, and median duration of treatment with control therapy was 3.9 months. The researchers noted that this was an investigator-assessed end point, which could mean the results are potentially subject to reporting bias. “Patients who crossed over from control therapy to receive olaparib had a shorter median duration of olaparib exposure (4.8 months) than those who were randomly assigned to receive olaparib (7.6 months). Thus, earlier treatment with olaparib may have an advantage over its use later in the disease course,” they wrote.

The safety profile of Lynparza appeared consistent with what was previously shown in the primary analysis. No cumulative toxic effects were observed during the extended exposure period.

Patients in the Lynparza group and those who crossed over to receive Lynparza reported anemia (39%), nausea (36%) and fatigue or asthenia (32%) as the most common side effects. Seven percent of patients discontinued Lynparza treatment because of anemia.

Patients with metastatic castration-resistant prostate cancer who had alterations in at least one of 15 prespecified genes with a direct or indirect role in homologous recombination repair (HRR) and whose disease had progressed during previous treatment with a next-generation hormonal agents were enrolled into the PROfound trial.

Group A consisted of 245 patients with at least one alteration in BRCA1, BRCA2 or ATM, while group B comprised 142 patients with at least one alteration in any of the other 12 prespecified genes.

Patients were randomly assigned to receive either olaparib or the physician’s choice of Xtandi or Zytiga. In group A, 162 patients received Lynparza twice daily and 83 patients were assigned to control therapy. In group B, 94 patients received the same Lynparza regimen while 48 patients were placed in the control arm.

Measuring imaging-based progression-free survival (PFS), or the time from the start of treatment until disease worsened, in group A was the primary goal of the study.

Imaging-based PFS was significantly longer in the Lynparza arm within group A compared with the control group (median, 7.4 months versus 3.6 months). In the initial analysis, a significant benefit was also observed with confirmed objective response rate and the time to pain progression.

“PROfound is the first positive phase 3 PARP inhibitor trial in metastatic castration-resistant prostate cancer, meeting its primary end point of prolonged radiographic progression-free survival for metastatic castration-resistant prostate cancer with alterations in BRCA1, BRCA2 or ATM progressing on prior next-generation hormonal agents and treated with olaparib versus with enzalutamide or abiraterone,” said Mateo, adding that these data continue to support 

the FDA’s approval of Lynparza in this setting

Articles

The PARP inhibitor Lynparza reduced the risk for death by 31% in men with metastatic castration-resistant prostate cancer compared with Xtandi or Zytiga plus the corticosteroid prednisone. 

Lynparza Significantly Improves Survival in Subset of Patients with Metastatic Prostate Cancer

Being proactive about one’s health is a key message this patient wants to share with others.

After working in the sun a lot, Bill had two lesions of cutaneous squamous cell carcinoma appear on his face that were treated with radiation. Shortly thereafter, he found a lump under his right arm and received a stage 4 diagnosis of metastatic cutaneous squamous cell carcinoma. After having been treated with another type of therapy, Bill's recent scans have shown improvement in his disease.

We spoke to Bill about his journey with cancer, how his caregiver and wife Cathie helped him through his diagnosis and treatment, and why it is important to be proactive about one’s health.

 After a walking trip in Portugal, we came back home and I discovered a lump in my right armpit. I was concerned because I couldn't understand why I was so fatigued in Portugal as we were doing this walking trip.

I went to our local doctor immediately and he did an ultrasound and said it was a large lump and referred me to a surgeon. Two weeks later, I went to the surgeon, he did an ultrasound, and he said, “Oh, my goodness, this thing is growing very fast. We need to take it out immediately.” So, within two days, I was in surgery and had the lump removed. And it took about two or three days for them to figure out what it was…But it came back as metastatic cutaneous squamous cell carcinoma, a type of skin cancer that has spread…I went and saw the oncologist.

He told me point blank, “You have stage 4 cutaneous squamous cell cancer…. Surgery, radiation, and chemotherapy are not options. There is a drug on the market that may help you.” My wife and I discussed the benefits and risks of this treatment option with my doctor and determined it was an appropriate treatment for me.

What went through your head when you received that diagnosis?

That was devastating. Thank goodness Cathie was there because she heard more than I could take in at the time. When somebody tells you that you have stage 4 cancer, you think it's all over and there is nothing you can do. Yeah, your head goes blank. It was pretty hard on me at that point.

What would you say is your biggest piece of advice for another individual who's facing this cancer diagnosis?

If you're in treatment, don't give up. Try and stay as positive as possible. It’s so important to not totally give up and have a good caregiver or somebody that will advocate for you, and talk to you and be on your side.

CURE spoke with a patient who was diagnosed with a type of skin cancer, called cutaneous squamous cell carcinoma, about his journey with cancer and why it is important to be proactive about one’s health.

Being Proactive About Skin Cancer

The Basics of Hairy Cell Leukemia

Seeking a Hairy Cell Leukemia Specialist

Joining a Hairy Cell Leukemia Clinical Trial

Promising Treatment Options in Hairy Cell Leukemia

Videos

CURE spoke with two physicians, on behalf of the Hairy Cell Leukemia Foundation, about the basics of the disease, as well as its diagnosis and treatment, and also about how patients can learn more about clinical trials.

Expanding the Horizon for Hairy Cell Leukemia

The treatment landscape looks bright for patients with skin cancer, especially with the medicine, technology and innovation going on in the space, according to Dr. Jeremy Brauer.

® spoke to Brauer, a spokesperson for the Skin Cancer Foundation, about the current treatment strategies in skin cancer, and how immunotherapy and targeted agents have been a “game-changer” for those with advanced disease.

“Immunotherapy and targeted therapies, more of these are going to be made available to individuals with metastatic melanoma as well as advanced squamous cell carcinoma,” he said, adding that patients should be sure to become educated about their disease and treatment options.

“Knowledge is power. A great resource is your board-certified dermatologist, and also the resources available on reputable web sites like the Skin Cancer Foundation and all of the literature they have available. Within dermatology, there is the American Academy of Dermatology and other societies that are great resources. I do believe it begins with education.”

Podcasts

In this episode of the “CURE Talks Cancer” podcast, we spoke with Dr. Jeremy Brauer, on behalf of the Skin Cancer Foundation, about current treatment strategies and the future of the disease.

Author | Kristie L. Kahl

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