Novel Immunotherapy Combinations in NSCLC

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The CTLA-4 inhibitor ipilimumab showed promising early results in a first-line phase II study for patients with non-small cell lung cancer (NSCLC) in combination with carboplatin plus paclitaxel, explains Everett E. Vokes, MD. In this trial, carboplatin and paclitaxel were administered along with placebo, concurrently with ipilimumab, or with phased ipilimumab after two cycles.

This trial was a proof of principle for checkpoint inhibition in NSCLC, explains Vokes. The phased treatment approach for ipilimumab is being investigated further in a definitive trial based on response rates in the phase II investigation. In this treatment approach, patients initially received two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin.

In addition to anti-CTLA-4 approaches, there is a phase I multiplex study under way that is examining the anti-PD-1 agent nivolumab in various combinations for patients with NSCLC, explains Vokes. One of the arms in this trial will explore nivolumab plus ipilimumab, a combination that demonstrated promising data in melanoma.

The most common adverse events associated with these immunotherapies are rash, diarrhea, nausea, headache, and pruritus, notes Anne S. Tsao, MD. Occasionally, serious adverse events, such as hepatitis, colitis, and fatal pneumonitis may also occur. As a result, vigilance is required when managing these side effects, Tsao notes.

These agents result in very unique immune-related toxicities that may require a multidisciplinary treatment team that includes an endocrinologist, believes Roy S. Herbst, MD, PhD. In general, if properly managed, the overall side effects associated with these agents are well tolerated.

There are currently two ongoing trials comparing nivolumab to docetaxel in patients with squamous and non-squamous metastatic NSCLC, points out Herbst. Also, in addition to treatment as a monotherapy, nivolumab shows potential as a backbone agent for combinations with cytotoxics and targeted therapies.

There is a great deal of potential for combinations with targeted therapies, specifically since the immunotherapies seem to impact not only the tumor cells but also the microenvironment, believes Karen L. Reckamp, MD, MS. Moreover, Vokes notes, the likelihood of achieving a cure increases as you treat patients in earlier stages. As a result, these agents may demonstrate the greatest potential in patients with minimal disease burden.