Lynparza as a Maintenance Treatment
- New data shows the promise of Olaparib (brand name Lynparza) as maintenance treatment in patients with newly diagnosed advanced (stages III or IV) ovarian cancer.
- Two trials found that the combination of two drugs (Lynparza and Avastin, also known as bevacizumab) may cut the risk of death by 38 percent.
- With the promising outcomes for those treated with PARP inhibitors, doctors are recognizing a huge curative potential for these new drugs. Still, transparent provider-patient discussions — about PARP-inhibitor eligibility, as well as the side effects and high prices associated with these drugs — are critically important.
Good news for women with ovarian cancer has just emerged from the European Society for Medical Oncology (ESMO) Annual Meeting. There was positive long-term data from two phase III trials of Olaparib (brand name Lynparza) as maintenance treatment in patients with newly diagnosed advanced (stages III or IV) ovarian cancer.
The trials found that the combination of two drugs (Lynparza and Avastin, also known as bevacizumab) may cut the risk of death by 38 percent. The data was based on results from a phase III clinical trial called PAOLA-1, and it revealed that women with ovarian cancer whose tumors were positive for a biomarker known as homologous recombination deficiency (HRD) could benefit from this drug combination.
An estimated 65.5 percent of Lynparza-Avastin takers are expected to be alive in five years, versus 48.4 percent for those only taking Avastin, according to investigators’ analysis of the phase III PAOLA-1 trial. The patients in the trials received the combo in the first-line maintenance setting after responding to a round of chemotherapy.
SurvivorNet spoke to Dr. Stephanie Wethington, an assistant professor of the Johns Hopkins Department of Gynecology and Obstetrics, who agreed with the importance of this new study. “The SOLO-1 [trial] is practice changing. The overall survivor data, which is what was presented at ESMO, is compelling and hints that waiting, ie treating at recurrence, is not as effective,” she said.
What are PARP Inhibitors?
Lynparza is a PARP inhibitor. The poly (ADP-ribose) polymerase, or PARP inhibitor drugs are relatively new to cancer care. These drugs, which are taken orally, work by preventing cancer cells that have been damaged, often by chemotherapy, from being able to heal themselves. PARP inhibitors have typically been used as maintenance therapy, to prevent a recurrence of cancer after a woman has already had surgery and traditional chemotherapy. When used this way, PARP inhibitors can potentially prolong remission and prevent disease recurrence for long periods of time – maybe even indefinitely.
The FDA also approved the use of PARP inhibitors for the frontline treatment of ovarian cancer, as well as in the maintenance setting. These drugs have typically been most effective in women with certain genetic mutations or markers, including BRCA mutations and homologous recombination deficiency (HRD) – a defect in the ability of a cell to repair its DNA.
The American Society of Clinical Oncology (ASCO) guidelines recommend PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stages III or IV ovarian cancer and have improved with chemotherapy.
Improving Progression-Free Survival
The PAOLA-1 trial presented at the European Society for Medical Oncology (ESMO) Annual Meeting was published on the European Cancer Journal. The study, which was conducted in 11 countries, evaluated the combination of Lynparza and Avastin on newly diagnosed, advanced (stages III or IV), high-grade ovarian cancer.
Women in the trial had all been treated with chemotherapy and Avastin, and then they either continued receiving Avastin with a placebo (inactive treatment), or with Lynparza.
The results showed that the greatest benefit was in patients with a BRCA mutation or HRD who received the combination of drugs. In patients with HRD-positive tumors who received Avastin plus Lynparza, the progression-free survival (that’s the time a relapsed patient’s cancer goes without growing) was just over 50 months, compared to 35.5 months in the group that received the placebo along with Avastin.
“We are seeing some tremendous progression-free survival benefits, and potentially almost a doubling of the progression-free survival,” Dr. David Engle, a gynecologic oncologist with the Baptist Medical Group in Memphis, told SurvivorNet in a previous conversation.
The researchers also demonstrated that the combination of Lynparza and Avastin may cut the risk of death by 38% in newly diagnosed advanced (stages III or IV) ovarian cancer patients.
SOLO-1 Trial
The SOLO-1 Phase III trial demonstrate that Lynparza provided a meaningful improvement in overall survival (OS) versus placebo in patients with BRCA-mutated newly diagnosed advanced ovarian cancer, reducing the risk of death by 45 percent. At the seven-year analysis, 67% of Lynparza patients were alive versus 47% of placebo patients. They also demonstrated that 45 percent of Lynparza patients versus 21% of placebo patients were alive and had not received a first subsequent treatment. These data provide the longest follow-up for any PARP inhibitor in this setting and support use of maintenance olaparib to achieve long-term remission and enhance the potential for cure.
Additional data showed median time to first subsequent therapy was 64 months with Lynparza versus 15.1 months with placebo. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials, with no new safety signals.
“Achieving long-term survival for patients with newly diagnosed advanced ovarian cancer is critical because the first-line setting offers the greatest potential to impact patient survival,” Dr. Paul DiSilvestro, investigator from the SOLO-1 trial, said in a statement. Dr. DiSilvestro is director of the Program in Women’s Oncology for Women & Infants Hospital of Rhode Island and Care New England Health System.
PARP Inhibitors Side-Effects
PARP inhibitors’ effects on the blood are among the most concerning to doctors. These drugs disrupt how cells repair damaged DNA, killing off tumor cells, but also some healthy cells as well. Bone marrow activity may be affected, which is why healthy blood counts — red blood cells, white blood cells, and platelets — may be diminished.
Hematologic (blood-related) side effects can include:
- Anemia (a drop in the red blood cells), which may result in fatigue
- Thrombocytopenia (a drop in the platelet count), which can cause easy bruising and excessive bleeding
- Neutropenia (a drop in the white blood cell count), which can leave people more susceptible to infection
In both trials presented, the safety data are encouraging. “One of the concerns with PARP inhibitors is the small risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML), particularly in patients with a BRCA mutation. The low levels of MDS and AML in both trials with longer follow-up is reassuring,” said Prof. Jonathan Ledermann, from UCL Cancer Institute, London, UK, at ESMO 2022.
Should PARP Inhibitors Be Prescribed to Everyone?
With the promising outcomes for those treated with PARP inhibitors, doctors are recognizing a huge curative potential for these new drugs.
Education and transparent provider-patient discussions about PARP-inhibitor eligibility, as well as the side effects and high prices associated with these drugs, can make a dramatic difference in treatment results.
Every patient has a different level of tolerance for side effects and financial burdens. So, although PARP inhibitors are giving many women with ovarian cancer a tremendous amount of hope, they still should not be universally prescribed.
