keep on trying...different regimens even beyond third line for Stage IV have effect!

[Lani]

35th European Society for Medical Oncology (ESMO) Congress


I previously reported a paper presented at the ASCO annual meeting on the diminishing returns from first vs second vs thirdline chemotherapy for Stage IV patients. In that paper, they said her2+ patients were the exception.

Now a paper @ ESMO is looking into who benefits most from fourth and more-line therapies.


In metastatic breast cancer, going beyond third-line chemotherapy can be successful in some patients, but identifying which subsets of patients have the best chance of benefit remains unclear

Findings from a new study, however, report that it may be possible to pinpoint which patients are most likely to benefit from subsequent lines of chemotherapy.

In a study presented here at the 35th European Society for Medical Oncology Congress, the only factor associated with a benefit from continued therapy was the duration of time to failure for each previous chemotherapy line.

The time to treatment failure for each line had a significant effect on the response rate and overall survival for subsequent treatment regimens (P < .001).

According to lead author Giovanni Bernardo, MD, PhD, who presented highlights of his study at a press briefing here, these results show that chemotherapy beyond the third line can be beneficial in patients who had responded to 1 or 2 prior chemotherapy regimens.

"These findings should help in the daily decision making of the optimal therapeutic strategy for the increasing number of fit women with metastatic breast cancer who ask for further treatment at the time of failure," said Dr. Bernardo, who is from the Fondazione Salvatore Maugeri–Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy.

"It could therefore be reasonable to propose subsequent active treatments in a targeted population with a good chance of response or stability, and correlated benefit for quality of life," he added.

Part of Decision-Making Process

Dr. Bernardo also emphasized that the final decision regarding continuation of therapy needs to be one that both the patient and physician jointly agree on. Together, they need carefully consider the expected benefit of the therapy, the effect of treatment-related toxicity on quality of life, the patient's preference and needs, and the psychological effect of not continuing treatment.

Fortunato Ciardiello, MD, PhD, professor at the Division of Medical Oncology, Seconda University of Naples, Italy, reiterated that the decision as to whether or not to continue treatment was one that is made between patient and physician. "Our interpretation of clinical trial results — and the personalization of the treatment — it is part of the process of making the decision," said Dr. Ciardiello, who moderated the briefing.

"This is an important piece of information that we should include when discussing treatment options with the patient," he said.

Benefit Dependent on Previous Response

Dr. Bernardo and colleagues conducted a retrospective analysis in a cohort of 980 women who received chemotherapy for metastatic breast cancer at their institution between 1992 and 2006. The median follow-up was 125 months (range, 48 - 192 months), and data for overall survival were updated on December 1, 2008.

The overall survival and time to treatment failure were calculated according to the Kaplan-Meyer method for each chemotherapy line that was administered, and a Cox proportional hazards model was used to identify factors that could influence response rate, time to failure, and overall survival.

The authors found that the median overall survival, which was evaluated from the first day of each chemotherapy line, decreased with each successive chemotherapy regimen. Survival with first-line treatment averaged 34.8 months (980 patients; range, 4 - 208 patients) and then decreased to 22.6 months with second-line therapy (838 patients), 14.6 months with third-line therapy (684 patients), 12.4 months for fourth-line therapy (302 patients), 9.4 months for fifth-line therapy (88 patients), and 8.2 months for 7 lines or more (45 patients).

The median time to treatment failure ranged from 9.2 months to 7.8 and 6.4 months for the first, second, and third line, respectively; there was no significant decrease observed beyond the third line (median, 5.2 months; range, 4.8 - 6.2 months).

In univariate analysis, several factors were positively linked to a longer duration of time to treatment failure for each chemotherapy line, including positive hormonal receptor status, absence of liver metastasis, exposure to adjuvant chemotherapy, and the response to treatment for metastatic disease.

In multivariate analysis, however, only the duration of time to treatment failure for each chemotherapy regimen had a significant effect on response rate and overall survival for subsequent treatments (P < .001).

The type of chemotherapy or the combination used did not appear to affect outcome in either univariate or multivariate analysis, the authors noted.

These results demonstrate that chemotherapy beyond the third line can provide effective benefit in patients who had responded to 1 or 2 prior regimens, conclude the authors. "These findings should help determine the appropriate strategy for proposing subsequent active schedules to the increasing number of fit women symptomatic for metastatic breast cancer who ask for further treatment."

All authors have disclosed no relevant financial relationships.

35th European Society for Medical Oncology Congress: Abstract 309P. Published October 10, 2010.

[Rich66]

It seems like this issue is directly tied to chemosensitivity testing...identifying helpful therapies in "difficult" patients.

I wonder how endocrine and chemo + endocrine therapies factor into this.

Do you hear anything about chemosensitivity testing? (rational therapeutics, chemofx etc)

[gdpawel]

There is no proven "standard" first line therapy which has been shown to be surperior to the many other choices which exist. The same situation exists in the setting of 2nd, 3rd, and 4th line therapy. The therapies are equivalent on a "population" basis, but not on an "individual" basis. Proven by the large number of patients who have progressive disease on 1st line therapy but who have good responses to 2nd or 3rd line therapy. These patients should have received the "correct" treatment in the 1st line setting.

From the people at ASCO.

If your first-line treatment does not work, starts but then stops working, or has side effects that you are unable to tolerate, your oncologist may recommend second-line treatment (if at first you don't succeed, keep on trying), which is a different treatment that may be another option for you. In some cases, you may be a candidate for third-line therapy or even additional rounds of treatment.

Of course, at any point in your treatment, ask your oncologist whether a clinical trial is an option. A clinical trial is a research study that tests a new treatment to prove it is safe, effective, and possibly better than the standard treatment you may already have had (in other words, you're a guinea pig). In some cases, participating in a clinical trial may be a better option for your second-line treatment than a standard treatment.

Oh! And one more thing. Don't worry, be happy! This is oncologist-approved cancer information from the American Society of Clinical Oncology.

http://www.cancer.net/patient/All+Ab...esn't+Work

[SunDiego]

Prolonging First-Line Chemotherapy Improves Outcomes for Patients With Metastatic Breast Cancer, Meta-Analysis Shows


http://www.sciencedaily.com/releases...1012101845.htm