CARE Lung Cancer Faculty Update from CLCCO 2013

Targeted Therapy and Testing at Diagnosis

Before the CLCCO meeting began on Friday February 8, 2013, there was a pre-meeting breakfast symposium that focused on targeted therapy and testing at diagnosis. What follows is a summary of the presentations made by Dr. Ken O’Byrne (St. James's Hospital and Trinity College, Dublin, Ireland) and Dr. Janessa Laskin (BC Cancer Agency) at the meeting.

Dr. O’Byrne opened his talk by introducing the importance of “targeting the target” when treating NSCLC.  He discussed how understanding the biological pathways underlying disease allows us to target interventions more effectively, even designing combination drugs with multiple “warheads” for complex diseases that are dependent upon on more than one underlying pathway and drugs that know how to hone in on the tumor or diseased tissue.

Discussion then moved to EGFR mutation as a predictive biomarker and Dr. O’Byrne outlined pivotal studies in which novel therapies are providing individualized patient treatments that maximize response rates, symptom control and survival. One of the key trials discussed was LUX-Lung 3: A Randomized, Open-Label, Phase III Study of Afatinib vs. Cisplatin/Pemetrexed as 1st-Line Treatment for Patients With Advanced Adenocarcinoma of the Lung Harboring EGFR-Activating Mutations. This trial showed how first-line treatment with afatinib, an orally available irreversible ErbB Family Blocker with high efficacy potential, can provide significant improvement in PFS (see Figure 1 below) compared to the traditional cisplatin/pemetrexed combination.

Figure 1. Primary Endpoint - PFS Common Mutations LUX-Lung 3

Figure 1. Primary Endpoint - PFS Common Mutations LUX-Lung 3

Dr. O’Byrne concluded his portion of the symposium by highlighting the importance of the integration of diagnostic tests into clinical practice. This flowed into Dr. Laskin’s presentation on the importance of molecular testing at the time of diagnosis.

Dr. Laskin began by introducing the CARE Program, which provides specialists, residents and junior fellows from across Canada an opportunity to gather and discuss key news and developments and frame information from a Canadian perspective. In 2011, the CARE program evolved into tumour specific working groups, including the CARE Lung Cancer Faculty.  The aims of the Lung Cancer Working Group are to consider lung specific issues with relevant educational outputs and collaboration.

Last year at CLCCO, the CARE Lung Cancer Faculty met and considered testing at diagnosis. The participants involved in this meeting agreed there was a need to extend and involve stakeholders along the patient pathway to successfully achieve ‘testing at diagnosis’. They concluded that respirologists and thoracic surgeons (respiratory medicine), as well as pathologists need to be involved.

Meetings were subsequently held with Canadian pathologists, respiratory medicine, and medical oncologists. There was a tacit agreement that:

Molecular status impacts patient outcome and influences treatment decision.

Testing at diagnosis allows for mutation status at first presentation.

Each of the Triads provided their perspective and frame-work to support testing at diagnosis within their specialty.

To continue improving testing at diagnosis, refinement of processes need to occur and all centers across Canada should be involved.

Based on the discussion at these meetings a CARE education toolkit was created to provide ‘Triad’ support at each centre. The toolkit was designed to encourage discussion around issues with current testing strategies and opportunities to improve, as well as to help encourage and support testing at diagnosis. Case studies were provided from key centers across Canada to provide a framework for testing at diagnosis for other Canadian centers to consider.

Figure 2: Simcoe Muskoka Regional Cancer Center testing algorithm

Figure 2: Simcoe Muskoka Regional Cancer Center testing algorithm

Dr. Laskin concluded her presentation by reviewing select case studies from key centers across Canada. Figure 2 is an example from the Simcoe Muskoka Regional Cancer Center case study (provided by Dr. Rob El-Maraghi). It shows the results of the collaboration effort between all of the major stakeholders, from the collecting of a pathology sample through to its handling and processing. Due to this collaboration, biomolecular testing has been made more accessible. In doing so, it can better assist with the clinical decision making at the time when it is most needed.

(This algorithm, along with the other case studies, are being reviewed by the CARE Faculty to serve as the basis for other centres to work from).

Key messages from both Dr. O’Byrne and Dr. Laskin’s presentations reiterated that translational biology should be at the core of new treatment development. To continue improving testing along the lung cancer care path, we must refine these processes and involve all centers across Canada.

The era for routine genotyping of NSCLC patients has arrived.