Expanded FDA Drug Approval Increases Lung Cancer Survivability, Hope for a Cure

Posted by Dr. Guneet Walia on October 9th, 2015

Nivolumab now approved for both squamous and non-squamous NSCLC patients
Diagnostic test to detect PDL1 expression also granted approval

October 9, 2015. The most common type of lung cancer, non-small cell lung cancer (NSCLC) is divided into two subtypes- squamous cell and non-squamous cell lung cancer- depending on the specific kinds of cells found in the tumors.

In March 2015, the US Food and Drug Administration (FDA) approved the first ever immunotherapy drug for lung cancer, Nivolumab (Opdivo marketed by Bristol Myers Squibb) for the treatment of patients with squamous non-small cell lung cancer whose disease progressed during or after platinum-based chemotherapy.

In another win for lung cancer patients, the FDA, acting three months ahead of schedule, today expanded the approved use of Opdivo to also treat non-squamous patients with advanced (metastatic) non-small cell lung cancer whose disease progressed during or after platinum-based chemotherapy.

Nivolumab is now the second immunotherapeutic agent to be approved by the FDA in little over a week for previously treated non-small cell lung cancer patients across all histologies-squamous or non-squamous, the first one being Pembrolizumab or Keytruda that was approved last Friday, October 2, 2015. The difference between the approvals for Pembrolizumab and Nivolumab is that Pembrolizumab has only been approved for use in patients with PDL1-positive tumors as determined by the PDL1 IHC 22C3 farmed companion diagnostic test, while PDL1 status testing is not mandated for the use of Nivolumab.  Further differences in the use of the two agents involve the schedules and dosing of the two immunotherapeutic medications, with Keytruda approved for administration every 3 weeks at 2mg/kg intravenously while Nivolumab being approved for use every 2 weeks at 3 mg/kg intravenously.

MECHANISM OF ACTION: Cancer cells use smart strategies to avoid immune recognition, attack, and tumor killing. One of these is the PD1-PDL1 pathway that is used by the body’s immune system to recognize ‘foreign’ cells such as tumors and mount an attack against them. Cancer cells ‘hijack’ the PD1-PDL1 pathway and avoid immune recognition. Nivolumab is an antibody that inhibits the protein PD1 (Programmed Death receptor 1) that is found on immune cells and some cancer cells. Inhibiting the PD1 protein takes the brakes off the immune system, allowing it to recognize cancer cells as ‘foreign’ and initiate an attack against them.

CLINICAL TRIAL: This approval from the FDA  for Nivolumab was based on the results of an international, randomized Phase 3 clinical trial, CHECKMATE- 057 that evaluated Nivolumab versus docetaxel chemotherapy in 582 previously treated metastatic NSCLC patients. Based on the impressive results of the immunotherapeutic agent, the trial was halted prematurely and patients on the control arm were offered the ability to cross over to the Nivolumab arm.

CHECKMATE-057 demonstrated superior overall survival benefit for Nivolumab vs. docetaxel in these patients who progressed on first line chemotherapy. The study showed that patients treated with Nivolumab lived an average of 12.2 months compared to 9.4 months in those treated with docetaxel. Additionally, 19 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, an effect that lasted an average of 17 months, compared to 12 percent among those taking docetaxel, which lasted an average of six months.

Role of PDL1 biomarker: Biomarkers are ‘measurable’ substances in the body whose presence is indicative of a phenomenon. Biomarkers of response are important in biology because they may help select patients most likely to respond to a therapy, avoiding both unnecessary financial and physical toxicity. The expression of the PDL1 ligand protein that interacts with the PD1 protein, may serve as a biomarker of response to immunotherapies targeted towards PD1. Nivolumab has been approved by the FDA in previously treated NSCLC patients regardless of their PDL1 status, however, an evaluation of samples from a subgroup of patients’ tumors suggests that the level of PD-L1 expression in NSCLC tumors may help identify patients who are more likely to live longer due to treatment with Nivolumab. Therefore, today the FDA also approved the PD-L1 IHC 28-8 pharmDx test to detect PD-L1 protein expression levels and help physicians determine which patients may benefit most from treatment with Opdivo. The PD-L1 IHC 28-8 pharmDx test is marketed by Dako North America Inc. in Carpinteria, California. It is important to note that PDL1 testing is not required for the use of Nivolumab, however, it may provide additional information that may be useful in treatment decision making.

SIDE EFFECTS: The most common side effects of Opdivo are fatigue, musculoskeletal pain, decreased appetite, cough and constipation. Immunotherapies also have the potential to cause serious side effects as a result of the modulation of the immune system, termed as immune-mediated side effects. Immune-mediated side effects observed with Nivlumab in this study were pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, encephalitis, other adverse reactions; infusion reactions; and embryofetal toxicity.

PRICE/ COSTS: Nivolumab (Opdivo) costs $12,500 per month or $150,000 per year.

ACCESS: Nivolumab is marketed by Bristol Myers Squibb (BMS). BMS Access Support®, the Bristol-Myers Squibb Reimbursement Services program, is designed to support access to BMS medicines and expedite time to therapy through reimbursement support as well as assistance for patient out-of-pocket costs. More information about our reimbursement support services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

It is an exciting time for lung cancer patients as we add new treatment strategies in our armamentarium to tackle this dreadful disease.

One Comment:
  1. Moodyone said:

    How can you call this “an exciting time for lung cancer patients” when this drug, like so many, is cost prohibitive?

    Not getting it to the patients that need it makes no sense at all to me, sorry.

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