Everything You Wanted To Know  about Olaparib  

Overview

Generic Name: olaparib oral capsules

Drug Class: Antineoplastics PARP Inhibitors

Olaparib Approval

FDA approves olaparib for adjuvant therapy of early breast cancer with high risk. On March 11, 2022, the Food and Drug Administration granted olaparib (Lynparza, AstraZeneca Pharmaceuticals, LP) approval for the adjuvant treatment of adult patients with high-risk early breast cancer who have had neoadjuvant or adjuvant chemotherapy and who have deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative tumors.

Olaparib Indications

Ovarian Cancer

Recurrent ovarian cancer

Recommended as a maintenance therapy for people who are in full or partial response to platinum-based chemotherapy and have recurrent ovarian cancer (including epithelial ovarian, fallopian tube, or primary peritoneal cancer), 300 mg PO BID

Continue until the condition worsens or the toxicity becomes intolerable

Advanced ovarian cancer (monotherapy)

300 mg PO BID is recommended as the first-line maintenance treatment for patients with deleterious or suspected deleterious somatic or germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have achieved full or partial response to first-line platinum-based chemotherapy.

Continue until the disease gets worse, the toxicity becomes intolerable, or the two years of treatment are up.

·    Patients who have fully recovered (with no radiologic evidence): Refuse treatment

·       Patients that have illness symptoms and may profit from ongoing care: Treatment after two years

 Advanced ovarian cancer (combination therapy)

Adults with advanced ovarian cancer who have completed or partially responded to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status, which is defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability, are recommended to receive this medication in combination with the drug bevacizumab as a first-line maintenance treatment.

For a total of 15 months, combine Olaparib 300 mg PO BID with Bevacizumab 15 mg/kg IV every three weeks (including with chemotherapy and as maintenance)

Continue until the disease gets worse, the toxicity becomes intolerable, or the two years of treatment are up.

For more details, consult the prescription information for bevacizumab when used with olaparib.

Advanced ovarian cancer (after ≥3 lines of chemotherapy) 

On August 26, 2022, the company voluntarily withdrew the indication in the United States. After the Phase III SOLO3 study's final overall survival analysis revealed a potential negative effect on overall survival for the olaparib-treated arm compared to the control arm in patients who received three or more prior lines of chemotherapy, the decision was made in conjunction with the FDA. Adults who have received three or more lines of chemotherapy prior to receiving olaparib for advanced gBRCAm cancer that is harmful or suspected to be harmful should not start taking it. Patients being treated for such an indication should be consulted and given information so they can decide on their future care.

Breast Cancer

High-risk early breast cancer

gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer in people previously treated with neoadjuvant or adjuvant chemotherapy is indicated for adjuvant treatment at 300 mg PO BID

Continue for a total of one year, or until the onset of unacceptable toxicity or the recurrence of the condition, whichever comes first.

Patients with positive hormone receptors taking olaparib According to current clinical practice guidelines, patients with HER2-negative breast cancer should continue receiving endocrine therapy concurrently.

Metastatic breast cancer

HER2-negative metastatic breast cancer and dreadful or probable dreadful gBRCAm are indicated conditions.

Patients who have received chemotherapy in the neoadjuvant, adjuvant, or metastatic context Patients with hormone receptor (HR)-positive breast cancer should have received endocrine therapy in the past or be regarded as inappropriate for endocrine therapy 300 mg PO BID

unless the disease becomes worse or the side effects become intolerable, keep on treating

Pancreatic Cancer

When the illness has not advanced after at least 16 weeks of first-line platinum-based chemotherapy, it is indicated for people with deleterious or suspected detrimental gBRCAm metastatic pancreatic adenocarcinoma. Unless the disease becomes worse or the side effects become intolerable, keep on treating. 

Metastatic Castration-Resistant Prostate Cancer

Recommended for people who have progressed after receiving treatment with enzalutamide or abiraterone for metastatic castration-resistant prostate cancer (mCRPC) with a deleterious or suspected harmful germline or somatic homologous recombination repair (HRR) gene mutation. 

Continue until the disease gets worse or there is intolerable toxicity. 

should have had a bilateral orchiectomy or should have received a gonadotropin-releasing hormone (GnRH) analog concurrently

Olaparib Mechanism Of Action

DNA single strand breaks (SSBs) are normally repaired by an error-free method using poly(ADP-ribose) polymerase (PARP). Double-strand breaks (DSBs) can happen during DNA replication when SSBs are present. The BRCA 1/2-mediated homologous recombination process, which is often thought of as an error-free repair mechanism, preferentially repairs them, while new data reveal that it may also be mutagenic. Olaparib prevents the PARP-mediated error-free repair of SSB, which causes synthetic lethality in cancer cells associated with the BRCA gene. This is because the DNA is then repaired with more error-prone repair mechanisms, single-strand annealing and non-homologous end joining. Large quantities of DNA damage, such as those caused by treatment with genotoxic chemicals, overwhelm these alternative repair systems. This leads to the accumulation of DSBs, incorrect DNA, and ultimately cell death.

Olaparib Lung Cancer

Therefore, researchers postulated that patients with metastatic non-small cell lung cancer who had only partially responded to treatment with platinum doublets could enrich for defective HRD, making their tumors more susceptible to the PARP inhibitor olaparib. 940 patients in all had their stage 1 eligibility determined, of which 263 had registered between February 24, 2014, and November 7, 2017. 70 patients were randomly assigned, 32 (46%) to Olaparib and 38 (54%) to a placebo after 194 people were excluded before stage 2 (due to no tumor shrinkage or as inevaluable). During induction therapy, 4% (3/70) of the randomly assigned patients had a complete response, and 96% (67/71) had a PR (or other signs of tumour response/mixed stability). The olaparib arm had a longer progression-free survival, but this difference was not statistically significant. A significant difference at the one-sided 0.2 level was seen when the progression-free survival hazard ratio was adjusted for smoking status and histology, indicating that tumour control may be possible for chemosensitive non-small cell lung cancer treated with PARP alone.

Olaparib In Ovarian Cancer

An amazing improvement in the treatment of ovarian cancer in women has been made with the introduction of OLAPARIB inhibitors. Olaparib is now licensed by the FDA for the maintenance treatment of BRCA-mutated ovarian cancer in both the recurrent and front-line settings, as well as the treatment of gBRCAm ovarian cancer in patients who have already had many rounds of chemotherapy. The importance of olaparib maintenance therapy for women with gBRCAm has been confirmed with the release of the SOLO1 and SOLO2 outcomes. It's significant that the only OLAPARIB inhibitor FDA-approved for use in patients with BRCA mutations is olaparib. Ongoing research will outline the function of olaparib in ovarian cancer and perhaps broaden its approved uses.

Olaparib in Prostate Cancer

After studies revealed that mutations in BRCA1 and BRCA2, as well as other genes involved in a cell's capacity to respond to DNA damage, may be present in about one-fourth of men with the condition, prostate cancer emerged as another strong possibility for Olaparib. Additional research connected these genetic alterations to a higher risk of developing prostate cancer as well as more aggressive disease.

Olaparib Side Effects

In the research, the most frequent Olaparib side effects were nausea, fatigue (including asthenia), anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, dysgeusia, dizziness, and stomatitis (10%).

Olaparib Side Effects are such as:

·       Hives,

·       Having Trouble Breathing,

·       Your Face, Lips, Tongue, Or Throat Swelling,

·       Fever,

·       Chills,

·       Weakness,

·       Lightheaded,

·       Tiredness,

·       Mouth Ulcers

·       Skin Lesions,

·       Simple Bruising,

·       Unexpected Bleeding,

·       Discomfort Or Burning During Urinating,

·       Blood In Your Stools Or Urine

·       Light Skin,

·       Chilly Feet And Hands,

·       Weight Loss,

·       Cough,

·       Wheezing,

·       Respiratory Difficulty,

·       Your Arm Or Leg Hurts Or Swells,

·       Respiratory Difficulty,

·       Sternal Pain,

·       Breathing Quickly, And

·       Rapid Heartbeats

Immediately seek medical attention if you experience any of the above symptoms.

The most typical Lynparza side effects include:

·       Low Blood Cell Numbers,

·       Discomfort And Burning After Urinating,

·       Unpleasant Urination,

·       Nausea,

·       Vomiting,

·       Upper Stomach Discomfort,

·       Diarrhea,

·       Heartburn,

·       Indigestion,

·       Decrease In Appetite,

·       Dizziness,

·       Weakness,

·       Tiredness,

·       Headache,

·       Cough,

·       Breathing Difficulties, And

·       Alternated Sense Of Taste

Olaparib Lynparza

Adults with advanced BRCA-mutated ovarian cancer can use the drug olaparib, which is marketed under the name Lynparza. It is a poly ADP ribose polymerase (PARP) inhibitor that prevents the enzyme from repairing DNA.