P3.CR-15 Squamous Cell Carcinoma Diagnosed While on Immunotherapy for Lung Adenocarcinoma: A Unique Clinical Case

In the first-line setting, pembrolizumab is used in non-small lung cancer (NSCLC), when the expression of PD-L1 is 50% or more, and the tests for EGFR, BRAF V600E mutations and ALK and ROS1 rearrangements are negative. In this setting, pembrolizumab showed higher response rates, overall survival benefit and fewer severe adverse events when compared with chemotherapy. Also, there is increasing evidence of the efficacy of immunotherapy in other types of cancer, namely, locally advanced unresectable or metastatic cutaneous squamous cell carcinoma (cSCC). A literature and patient clinical information review was performed. A 72 years-old man, former smoker (60 pack-year), was admitted to our hospital for treatment of a stage IIIA (cT1N2M0) lung adenocarcinoma, diagnosed in November 2015 following screening exams. Concurrent chemoradiotherapy was administered between 7th January and 14th February 2016 (70Gy in 35 fractions, using Intensity-modulated radiation therapy technic with carboplatin-paclitaxel duplet) followed by consolidation chemotherapy. Ten months later, a sub-carinal adenopathy recurrence confirmed by biopsy was diagnosed. The tumor was highly positive to PD-L1 (expression over 90%) and showed no predictive mutations/rearrangements of sensitivity to molecular target EGFR, ALK or ROS1 drugs. Radical radiotherapy to the mediastin was administered between 9th January and 17th February 2017 (60Gy in 30 fractions, using volumetric modulated arc radiotherapy technic). Metastatic disease was diagnosed 7 months later, with right hilar and mediastinal adenopathies, bilateral pulmonary nodules and right pleural metastasis. Pembrolizumab 200mg every 21 days was initiated in 10th November 2017 until 20th March 2018 (7 cycles), due to disease progression and to grade 3 xerostomia (CTCAE v4.03). Second-line palliative treatment with platin-pemetrexed duplet was proposed. In January 2018, while on pembrolizumab, the patient noticed an ulcerated and growing lesion in the right ala of the nose. The lesion was surgically removed in 29th March 2018, with the diagnosis of an invasive cSCC. The patient developed a cSCC while on treatment with pembrolizumab for metastatic lung adenocarcinoma. The reason for this does not seem to be associated with immunotherapy as there is no current description in the literature of development of second neoplasia while on immunotherapy. Innate resistance to immunotherapy could be a possible explanation, with unsuccessful reactivation and poor clonal-proliferation of antigen-experienced T cells present in the tumor micro-environment.