Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?

Olaparib May Be Option For Certain Patients With Biochemically Recurrent Prostate Cancer

Olaparib monotherapy may be a treatment option for some patients with high-risk biochemically recurrent prostate cancer, according to researchers.

The researchers found that olaparib could produce a 50% or higher decline in prostate-specific antigen (PSA) from baseline (PSA50 response) in some patients, but olaparib did not "have sufficient activity" in patients without homologous recombination repair (HRR) alterations. These findings were published in JAMA Oncology.

Researchers tested olaparib in a phase 2 trial (NCT03047135) of 51 patients with high-risk biochemically recurrent prostate cancer who had undergone radical prostatectomy. At baseline, the patients' mean age was 63.8 years, the median PSA was 2.8 ng/mL, and the mean PSA doubling time was 2.9 months. Twenty-seven patients had HRR alterations. The median time from surgery to study entry was 4.8 years.

On study, the patients took olaparib at 300 mg twice daily until doubling of baseline PSA, clinical or radiographic progression, or unacceptable toxicity.

Overall, 26% of patients (13/51) had a PSA50 response. There were no PSA50 responses in the HRR-negative group. In the HRR-positive group, the PSA50 response rate was 48% (13/27).

All 11 patients with BRCA2 alterations had a PSA50 response. The other responses occurred in a patient with a CHEK2 alteration and a patient with an ATM alteration.

The median PSA progression-free survival (PFS) was 19.3 months in the overall cohort. The median PSA PFS was 22.1 months in the HRR-positive group and 12.8 months in the HRR-negative group (hazard ratio [HR], 0.80; 95% CI, 0.33-1.97; P =.61).

In the sensitivity analysis using restricted mean survival time over 36 months, the PSA PFS was 19.3 months in the HRR-positive group and 8.5 months in the HRR-negative group (P =.001).

The median metastasis-free survival (MFS) was 32.9 months overall. It was 41.9 months in the HRR-positive group and 16.9 months in the HRR-negative group (HR, 0.53; 95% CI, 0.23-1.18; P =.12).

In the sensitivity analysis using restricted mean survival time over 36 months, the MFS was 28.9 months in the HRR-positive group and 19.6 months in the HRR-negative group (P =.02).

The median time to next anticancer therapy was 15.4 months overall. It was 22.7 months in the HRR-positive group and 12.4 months in the HRR-negative group (HR, 0.43; 95% CI, 0.21-0.90; P =.02).

The most common adverse events (AEs) were fatigue (63%), nausea (55%), and leukopenia (43%). Three patients stopped taking olaparib due to treatment-related AEs (2 due to anemia and 1 due to leukopenia). There were no on-trial deaths.

Based on these findings, the researchers concluded that molecularly targeted therapies "may be a reasonable treatment strategy for some patients with recurrent prostate cancer."

Disclosures: This research was supported by AstraZeneca, Veracyte, Foundation Medicine, and government grants. Some study authors disclosed conflicts of interest. Please see the original reference for complete disclosures.

This article originally appeared on Cancer Therapy Advisor

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After A Scottish Aye, NICE Says No To Lynparza For Prostate Cancer

AstraZeneca's PARP inhibitor Lynparza should not be made available routinely on the NHS n England and Wales as a treatment for prostate cancer, according to cost effectiveness agency NICE.

That is the conclusion of draft guidance which says that the evidence for Lynparza (olaparib) as a treatment for prostate cancer is uncertain, and therefore not a good use of NHS funds.

The decision – which comes after an earlier rejection by NICE in March 2021 – covers Lynparza's approval for prostate cancer cases with BRCA1 or BRCA2 mutations that has spread (metastasised) to other parts of the body and has relapsed after prior treatment with the hormonal drugs abiraterone or enzalutamide.

It creates a misalignment of policy around the UK for Lynparza in prostate cancer, as Scotland approved use of the drug in this setting last September.

The stumbling block for the evidence presented by AZ in support of Lynparza was that it compared the drug to re-treatment with abiraterone or enzalutamide, which is not standard care in the NHS.

Studies showed men taking Lynparza had more time before their disease gets worse and live longer overall than those retreated with abiraterone or enzalutamide, acknowledged NICE.

However, these patients generally receive chemotherapy with Sanofi's Jevtana (cabazitaxel) or docetaxel, or Bayer's radiopharma drug Xofigo (radium233-dichloride).

There is indirect evidence to suggest Lynparza increases overall survival  compared to cabazitaxel, the data is "uncertain," according to NICE, and there is no comparative data with docetaxel and Xofigo.

NICE's chief executive Gillian Leng said the agency was "disappointed not to be able to recommend olaparib for use in this way," but added that "the company's own economic model demonstrated that the drug does not offer enough benefit to justify the price it is asking."

The list price of Lynparza is £2,317.50 per pack of 56 tablets (14 days' supply), making the cost of an average treatment course £37,491, although AZ provides the drug to the NHS at a confidential discount. The drug is approved for NHS prescribing in other indications including for ovarian cancer.

AZ  issued this response to the NICE statement on the decision: "It is our firm belief that the economic model and analyses are cost-effective when our commercial offer, aligned to that made in Scotland, is taken in to account. This same evidence base and modelling was sufficient to secure access in Scotland."

The company added that it is "committed to working with NICE and NHS England to ensure patient access for this effective treatment in an area of high unmet need."

The Institute of Cancer Research (ICR) in London, which was involved early on in the development of the PARP class, said it was also disappointed by the outcome of the second appraisal.

[caption id="attachment_86282" align="alignright" width="180"] Professor Johann de Bono[/caption]

"I was delighted when olaparib was approved for NHS patients in Scotland earlier this year – and it's disappointing that this decision means their counterparts in England and Wales will miss out on such a valuable new treatment option," said ICR's Prof Johann De Bono, who led the PROfound trial of Lynparza in relapsed prostate cancer.

"It's an example of the barriers that exist to making innovative drugs available at prices that the NHS can afford and is going to result in postcode prescribing across the UK," he added.

The ICR has urged AZ and NICE to reach an agreement on the price of Lynparza that will allow it to be used in England and Wales.

"We must also address the systemic issues we face in providing NHS patients with access to innovative cancer drugs at appropriate prices," said ICR's chief executive Prof Kristian Helin.

"The NHS needs to show more flexibility in the way drugs are priced from one indication to the next, to ensure new drugs can reach more patients, and pharmaceutical companies in return must be prepared to offer discounts if drugs do not work as well as promised," he added.

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