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New Findings on Cancers Affecting Women

  1. Top of page
  2. New Findings on Cancers Affecting Women
  3. Dr. Kohn on CA125
  4. Dr. Meric-Bernstam on PARP

Experts express concern about CA125 testing and hope for PARP inhibitors

Several treatment advances in breast and gynecological cancers were announced during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June. Among them were:

CA125 Levels not a Good Touchstone for Ovarian Cancer Relapse

Many women who undergo treatment for ovarian cancer worry that they could have a relapse. As a result, they often have frequent blood tests for CA125, a marker of growth for ovarian and other cancers, according to the study's lead author, Gordon Rustin, MD, professor of oncology at Mount Vernon Cancer Center in Hertfordshire, United Kingdom. In fact, researchers found that there was no benefit to early chemotherapy and that patients could avoid the inconvenience and anxiety of frequent retesting for CA125.

Researchers compared overall survival between 265 women with ovarian cancer in remission after initial chemotherapy who began second-line chemotherapy after experiencing a rise in CA125 and 264 women with rising CA125 whose treatment was delayed until symptoms of relapse appeared (ie, pelvic or abdominal pain, bloating, frequency or urgency of urination, and difficulty eating or feeling full quickly).

The early treatment group started chemotherapy an average of 5 months before the delayed-treatment group; regardless, the overall survival was the same in both groups—41 months since completion of first-line chemotherapy. The authors say women can be reassured that they can delay treatment until symptoms develop.

The Ovarian Cancer National Alliance expressed concern over the study, noting that the results are far from reassuring to ovarian cancer survivors. The group stated in a news release that CA125 and CA125+HE4 are both approved by the Food and Drug Administration to monitor recurrence. They added that even without symptoms, a rising CA125 may result in further tests such as an MRI or PET scan,which will detect the disease.

Robert Bast, Jr, MD, vice president for translational research at the University of Texas M. D. Anderson Cancer Center in Houston, developed the CA125 test. He notes that it is crucial for women to continue to have the choice of monitoring their disease status. Also, some patients may want to start novel treatments 5 months earlier in an effort to fight their recurrent cancer, he says.

Dr. Bast adds that data from the study could be misinterpreted because physicians participating in the study were not required to use a single therapeutic protocol. Instead, they determined on their own which chemotherapy to use.

“The majority of women did not receive optimal chemotherapy at the time of disease recurrence,” he says.

Karen Orloff Kaplan, CEO for the Ovarian Cancer National Alliance, adds that although CA125 may not be completely accurate in many women, it has shown promise in others. “Our hope is that these new findings will serve as a catalyst to the research community and those who fund their work [for redoubling] their efforts to find an early detection test and more effective treatments,when survival rates are highest,” she concludes.

PARP Inhibitors for Hard-to-Treat Breast Cancers

Two studies looked at the effectiveness of poly (AdP-ribose) polymerase (PARP) inhibitors on hard-to-treat breast cancers: “triple negative” and BRCA1-2-deficient breast cancers. Cancer cells use the PARP enzyme to repair DNA damage, including that caused by chemotherapy. Researchers are trying to determine whether drugs that inhibit this enzyme will make cancer cells more responsive to treatment.

Dr. Kohn on CA125

  1. Top of page
  2. New Findings on Cancers Affecting Women
  3. Dr. Kohn on CA125
  4. Dr. Meric-Bernstam on PARP

Comments from Elise Kohn, MD, section editor of gynecologic oncology for Cancer.

Intuitively one might argue, and the community has accepted on faith, that rising CA125 heralds recurrence and that early treatment at a presumed low tumor burden is better. This randomized trial involving 59 institutions in 10 countries (not the United States) found no survival differences. Further, researchers demonstrated that there was a greater overall chemotherapy exposure and a worse quality-of-life measure in women treated by CA125 criteria and not by symptoms.

Over time, the medical community has leaned heavily on theCA125 test and turned frompathologic, and noweven radiographic, documentation of first (or subsequent) recurrence of ovarian cancer. Because both biopsy and imaging can be stressful to the patient, the patient community has come to accept and expect that approach. This has created “an addiction” to the CA125 value as a therapy determinant.

This important trial has reminded us to use our tools of listening and examination and not to rely heavily on a single, albeit easy,measurement. It suggests that perhapswe have jumped too early and too often in our zeal to help our patients minimize tumor burden and tumor-related injury. Also, it is important for us to educate our patients and their families about the meaning of CA125. If our patients have increasing CA125 levels, we need to tell them we share their concerns and that we will monitor them closely and will institute therapy when the time is right.

Dr. Meric-Bernstam on PARP

  1. Top of page
  2. New Findings on Cancers Affecting Women
  3. Dr. Kohn on CA125
  4. Dr. Meric-Bernstam on PARP

Comments from Funda Meric-Bernstam, MD, section editor of breast disease for Cancer, and associate professor of surgical oncology at the University of Texas M. D. Anderson Cancer Center in Houston

Since the seminal preclinical reports that BRCA-deficient tumors specifically benefit from inhibitors of PARP, the oncology community has been enthusiastically awaiting the clinical results from PARP inhibitors.1,2 ASCO2009 included 2 important presentations that showed preliminary evidence of clinical activity of PARP inhibitors. One study, by Tuttetal, was an international, multicenter, proof-of-concept study and showed that in patients with confirmed BRCA1/2 mutations and chemotherapy- refractory breast cancer, high doses of the oral PARP inhibitor olaparib (AZD2281) is well tolerated and has clinical benefit.3

The second study, by O'Shaughnessy etal, showed that the PARP inhibitor BSI-201, in combination with gemcitabine/carboplatin showed improved survival comparedwith gemcitabine/carboplatin alone in a randomized phase 2 trial in metastatic triple-negative breast cancer.4 These studies, although preliminary, are extremely promising.

If confirmed in phase 3 trials, PARP inhibitors are likely to become an important new treatment for patients with triplenegative disease as well as BRCA1 and 2 mutations. The efficacyintriple- negativediseaseunselectedforBRCAmutations emphasizesthatmanypatientswithtriple-negativebreastcancerwithout known BRCA genomicmutations likely have other aberrations in DNA repair, contributing to their sensitivity to PARP inhibitors. Furtherwork is needed to determinemolecular predictors of sensitivity to this newclass of drugs, the best combinations, and the long-term effects of these agents.

References

1. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumors with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434: 913–917.

2. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCAmutant cells as a therapeutic strategy. Nature. 2005;434:917–921.

3. Tutt A, Robson M, Garber JE, et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer [abstract]. 2009 ASCO Meeting Proceedings:CRA501.

4. O'Shaughnessy J, Osborne C, Pippen J, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial [abstract]. 2009 ASCO Meeting Proceedings:3.