For years, the traditional treatment for newly diagnosed advanced non-small cell lung cancer (NSCLC) has been chemotherapy doublets – carboplatin-paclitaxel, cisplatin-docetaxel, carboplatin-gemcitabine etc so by the time patients progress to second line therapy they will be fairly beaten up and overall survival for the disease is sadly only a year or so for many patients. Chemotherapy has the disadvantage
Recent years have seen the advent of targeted therapies in NSCLC including Iressa, Tarceva and Avastin. Tarceva (erlotinib), an EGFR inhibitor, and Avastin (bevacizumab), a VEGFR inhibitor, are both produced by Genentech and Roche so it was inevitable that they would be combined at some point to see if the combination would be effective as maintenance therapy. It makes strong scientific sense to determine if it makes good sense to try to combat the cancer by treating both the
cancer cell’s growth and division signaling pathways (Tarceva) and
the supporting microenvironment by reducing the tumor blood supply (Avastin) as shown graphically below:
Yesterday, I spotted this item in my feed reader with the sensationalist headline of screaming, "Avastin-Tarceva combination fails in lung cancer"! Instead of purchasing the item, I checked out the company websites for more information. Lo and behold there was better information there on the two front-line trials that were investigating the combination.
The ATLAS trial was designed to see if Avastin with or without Tarceva as maintenance therapy was effective in squamous NSCLC patients after 4 cycles of standard chemotherapy with Avastin (every 3 weeks). According to Genentech and Roche:
significant toxicity, patients were then randomized (n=768) to receive
maintenance therapy with Avastin plus Tarceva or Avastin plus placebo
until disease progression."
The study met it's primary endpoint, progression free survival (PFS). This means that Avastin and Tarceva in combination significantly improved the time patients with advanced lung cancer can live without their disease worsening.
A previous trial (SATURN), looked at the benefit of adding Tarceva as maintenance therapy after standard chemotherapy in NSCLC patients. The study reported that Tarceva significantly delayed disease progression compared to placebo.
These results offer new hope for lung cancer patients.
If patients have a squamous histology, they can be treated with 4 cycles of standard chemotherapy with Avastin, then Tarceva plus Avastin or Tarceva alone as maintenance therapy, while non-squamous patients can receive Tarceva therapy since Avastin is not suitable for those with a non-squamous histology due to increased risks of GI bleeding.
As for that Nature snippet on failure in second-line? Well, it makes more sense to treat with targeted therapies up front before the tumour burden is too great and the drugs will have a better chance of working. Competitively, this may also mean that the bar is raised for new entrants in first line NSCLC and Alimta and Taxotere will see more second line use going forward. The improved time to progression will also mean a delay in second line treatment.
All in all, these results are positive and we can expect that:
to be presented at the forthcoming ASCO meeting in June
Genentech and Roche to be discussing adding label extensions with the
FDA and EMEA.