Struggles in Finding a Second-Line Chemotherapy Treatment for Mesothelioma

A recent study displayed as part of a poster presentation at the European Lung Cancer Conference 2016 (ELCC) showed that there has been little success in finding an effective 2nd-line chemotherapy treatment for mesothelioma. The study followed 98 mesothelioma patients (pleural and peritoneal) at the University of Athens in Greece, ultimately concluding that there is still no satisfactory second-line chemotherapy treatment for patients who have mesothelioma.

The Importance of Second-Line Treatments

According to the National Cancer Institute, a second-line treatment is administered to patients when the initial treatment (also called “first-line treatment”) doesn’t work or stops working as expected. This can happen for a number of reasons:

Patient response: Reactions to certain types of treatment can vary greatly depending on a person’s genetics, health history, type of mesothelioma, and other factors. This is especially true with broad, systemic treatments like chemotherapy. Although first-line treatments are the most likely to be effective against cancer, given the wide variation in patient responses, some chemo drugs are simply less effective for some people than others.

Recurrence: Sometimes cancer comes back tougher and stronger the second time around. When recurrence happens, first-line treatment may not be as effective as it was the first time around, which would require a second-line treatment.

Diminishing returns: Over time, drugs can simply stop working as well as they used to. This can be due to toxicity levels – that is, build-up of the drug in the system – or an increased tolerance by the body, among other factors.

In light of each of these reasons, finding an effective second-line chemotherapy treatment for mesothelioma is extremely important.

Existing Second-Line Mesothelioma Treatments

The University of Athens study took a look at the effectiveness of existing second-line chemotherapy treatments for mesothelioma. In particular, researchers looked at three specific chemotherapy drug combinations that are often used as second-line treatments:

• Taxanes and gemcitabine
• Docetaxel
• Pemetrexed (alone or in combination with a platinum-based drug)

The study observed 98 patients who received one of these second-line treatments. While there was some variation in outcomes – those who took pemetrexed (Alimta) had a slightly longer survival time – the researchers concluded that the reproducibility and interpretation of the results were not possible.

Ultimately, none of the treatments studied provide a consistently reliable option for second-line chemotherapy. The researchers concluded that “no satisfactory second-line chemotherapy agent exists for patients with mesothelioma.”

The Search for Second-Line Treatment Continues

Although this particular study was unable to find a reliable second-line treatment for mesothelioma, researchers are continuing to look for more effective ways to treat the disease if the first-line treatment fails.

One such study, published earlier this year, looked at patients with malignant pleural mesothelioma that could not be removed surgically. This study used an immunotherapy drug (adenovirus interferon-alpha2b) as first-line treatment, followed up by a second-line treatment of chemotherapy. The study concluded that this order of treatment was generally successful: “Overall survival rate was significantly higher than historical controls in the second-line group.” The researchers plan to move on the a larger clinical trial to further study the effectiveness of using chemotherapy as a second-line treatment after immunotherapy.

Nonetheless, the current landscape is bleak when it comes to second-line therapies. A review of literature published this past April, which looked at a number of previously published studies, concluded, “The efficacy of second-line therapy remains unanswered at present and it is still an unmet need in this patient population.” That said, the review notes that the use of higher doses of pemetrexed through pemetrexed maintenance treatment (PMT) “appears extremely promising,” showing that we may be coming closer to an effective second-line treatment.