Current and Emerging Therapies in NSCLC - Episode 5

Case Study: Second-Line Treatment of Adenocarcinoma

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In a case-based discussion, moderator Corey J. Langer, MD, describes a 46 year-old patient with a diagnosis of non-squamous, non-small cell lung cancer that is negative for mutations in EGFR, ALK, ROS1, and KRAS. The patient received an initial pemetrexed-containing regimen followed by maintenance bevacizumab along with zoledronic acid for 6 months. At this point, the patient progressed with bone metastases.

Docetaxel or erlotinib are potential treatment options in the second-line setting, suggests Roy S. Herbst, MD, PhD. However, utilizing erlotinib in the absence of an EGFR mutation doesn't demonstrate additional benefit, adds Herbst. However, for patients without an EGFR mutation, the VeriStrat test can be used to help predict response based on blood-based proteins.

In the phase III PROSE trial that examined the test, patients categorizes as good had similar survival outcomes when treated with erlotinib and chemotherapy. However, those with a poor status, benefit more from chemotherapy than erlotinib. Proteomic-based classifiers could help determine appropriate treatments; however, the VeriStrat test may still require further validation, Herbst believes. As a result, Herbst suggests utilizing docetaxel as a second-line treatment.

The PROSE trial did not indicate that VeriStrat was a positive predictor for benefit from erlotinib but it did suggests patients who would not benefit, Anne S. Tsao, MD adds. Moreover, many of the prognostic groups identified by the test coincided with other identifiable clinical factors. However, looking at the full picture, Herbst believes the limited benefit demonstrated by both docetaxel and erlotinib stresses the importance of new drug development in this setting.

Another options, Langer suggests, would be to readminister the initial carboplatin and pemetrexed regimen. This could represent an effective option, particularly if the initial response was high and the treatment was well tolerated, believes Everett E. Vokes, MD. Outside of this, docetaxel would make an excellent choice.

The continuation of bevacizumab after first-line treatment is an established paradigm for patients with colorectal cancer, notes Langer. However, many approaches that work in other disease types have not successfully translated to the management of NSCLC, adds Karen L. Reckamp, MD, MS. As a result of this, to investigate the efficacy of continued bevacizumab specifically in nonsquamous NSCLC, the phase IIIb AvaALL trial was formed and is currently in progress, notes Langer.