Clinical Progress and Treatment

• September 2016: Brain MRI showed no evidence of central nervous system disease.
• October 2016: CT of chest/abdomen/pelvis (C/A/P) showed stable disease in lung.
• Good performance status
• November 2016: Rash worsened to involve upper chest, back and extremities (doxycycline 100 mg).
• December 2016: Mid-cycle 6 of erlotinib +/- VEGF inhibitor – CT of C/A/P demonstrated radiographic progression in the lung and mediastinum.
• Removed from study protocol
• Recommendation for repeat bronchoscopy with tumor biopsy to assess T790M status (3 to 5 cores requested)
• December 2016: Because of increased pain in the jaw, patient underwent a CT of the soft tissue of the neck.
• Osseous destructive mass involving the anterior left mandibular body
• 2.4 cm x 8.0 cm in greatest orthogonal axial dimensions and 1.4 cm in craniocaudal dimensions
• Level I lymphadenopathy
• December 2016 – January 2017: Palliative radiation therapy to left hemimandible (30 Gy in 10 fractions)
• December 2016: Endobronchial ultrasound with needle biopsy (22-gauge; four samples were obtained)
• Continued presence of EGFR L858R mutation, but no T790M
• December 2016: Signed informed consent to allow recent biopsy sample to be sent for large panel genomic testing
• Forthcoming treatment considerations: systemic chemotherapy (carboplatin/pemetrexed) vs. immunotherapy vs. ASCO clinical trial TAPUR (https://www.tapur.org/)
• January 2017: Developed mucositis from radiation therapy
• January 2017: Case was discussed at institution’s molecular tumor board.
• BRAF/KRAS/NRAS wild-type – matched to cetuximab (Erbitux, Eli Lilly) on TAPUR
• ATM - matched to olaparib (Lynparza, AstraZeneca) on TAPUR but requires ASCO TAPUR molecular tumor board reviewed
• PD-L1 tumor proportion score (TPS) – 100%
• January 2017: Treatment recommendation was to start pembrolizumab (Keytruda, Merck), an anti–PD-L1 therapy, based on patient's high PD-L1 TPS.
• February 2017 – April 2017: Tolerating pembrolizumab well with minimal adverse effects
• April 2017: Restaging CT of chest, soft tissue neck demonstrating partial response
• Brain MRI revealed a new enhancing intraparenchymal mass in the right frontal lobe of brain (14 mm x 7 mm x 11 mm).
• Referral to radiation oncology for stereotactic radiosurgery (SRS)
• May 2017 – June 2017: SRS to right frontal lobe lesion; pembrolizumab was continued.
• June 2017: Restaging CT scans demonstrating disease progression
• Right hilar mass increased.
• Brain MRI identified second lesion that was too small to pick up on prior scan.
• Decrease in size of other brain lesion
• July 2017: Palliative radiation therapy to right hilar mass
• July 2017: Liquid biopsy was performed.
• If T790M present, options include osimertinib (Tagrisso, AstraZeneca).
• T790M was not detected using Roche cobas EGFR Mutation Test v2. L858R mutation was identified.
• August 2017: Restaging scans showed no new sites of disease.
• CT of abdomen demonstrated increasing adrenal gland mass and increasing size in left sacral mass.
• Brain MRI was stable.
• August 2017: Initiated third-line treatment with carboplatin/pemetrexed
• September 2017: Palliative radiation to left sacrum
• September 2017: Cycle 2 was held to recover from small bowel obstruction and radiation.
• October 2017: Restaging CT of chest was stable.
• October 2017 – November 2017: Continued carboplatin/pemetrexed
• November 2017: Restaging scans
• Brain MRI showed slight enlargement of left precentral gyrus lesion (3 mm → 5 mm).
• CT of abdomen showed increasing size of left adrenal gland. CT of chest showed stable disease.