Physician:

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Sandeep Sehdev, MD, FRCPC
Medical Oncologist at William Osler Health System, Etobicoke, Ontario

Presentation:

  • A 52-year-old female who had never smoked.
  • Patient had no past medical history, no regular medications, and no allergies.
  • She presented with cough, fatigue, shortness of breath, and weight loss of 2 kg.

Laboratory and Clinical Findings:

  • CBC and blood chemistries revealed a hemoglobin count of 105 g/L, but were otherwise normal.
  • Chest X-ray revealed a left suprahilar fullness and two right nodules of 1-cm each.
  • CT scan revealed a 3.5-cm spiculated left lung mass, hilar adenopathy, and multiple bilateral lung metastases (ranging 6–12 mm).
  • Brain MRI was negative for metastases.
  • Bone scan revealed metastases at the 6th thoracic vertebra and the left 9th rib.
    CT-guided biopsy of the left lung mass confirmed adenocarcinoma and mutational analysis established the presence of an activating EGFR mutation (L858R).

Diagnosis:

  • Based on imaging, lung biopsy, and molecular testing findings, the patient was diagnosed with EGFR M+ (L858R) metastatic adenocarcinoma of the lung.

Treatments, Outcomes, and AE Management:

  • Gefitinib (250 mg PO OD) was prescribed.
    • The patient exhibited early grade 1 rash and pruritus; rash was treated with topical emollients, reassurance, and observation.
    • At one month, the patient achieved PR and had improved shortness of breath and cough.
    • At 2 months, patient had SD and the rash had started to resolve from the face; however, patient had more torso erythematous patches and pruritus. At this stage, topical low-dose corticosteroid was prescribed.
    • At 4 months, patient had minor progression; gefitinib was continued and rash improved.
    • At 6 months, patient had PD with enlarging as well as new lung lesions and also developed back pain.
  • Palliative radiation therapy was given to T6 vertebral metastases (20 Gy in five fractions, while gefitinib was held).
  • Chemotherapy (carboplatin and pemetrexed for four cycles) was administered.
    • The next CT scan revealed SD.
    • Pemetrexed maintenance was administered.
      • After three cycles on maintenance, patient had PD with enlarging but not new lung lesions; she also had two new liver metastases that were a maximum of 2.2-cm each.
  • Afatinib (30 mg PO OD) was prescribed via the compassionate access program.
    • Patient was also prescribed prophylactic minocycline (100 mg PO BID) for six weeks.
    • At one month, a chest X-ray revealed SD; patient also had grade 1 rash, but less then when she was on gefitinib. As a result, afatinib dose was escalated to 40 mg PO OD.
    • At 2 months, CT scan revealed a minor response (not quite PR by RECIST); patient also had grade 2 rash and grade 1 diarrhea.
  • Afatinib dose was reduced to 30 mg PO OD and patient was given loperamide when necessary; rash and diarrhea resolved and patient only had pruritus and fatigue.
    • At 4 months, a CT scan revealed PR.
    • At 8 months, patient had minor progression but was asymptomatic.
    • At 9 months, her cough became more severe.
  • When on afatinib, rash and diarrhea were the most prevalent AEs; no AEs were grade 3 or 4, but they were affecting patient’s quality of life and activities of daily living.
    • Patient was willing to continue her treatment even when AEs were present.
  • Nivolumab (3 mg/kg iv q2w) was prescribed.
    • Patient has had six treatments so far and has exhibited SD with no toxicities.

Conclusion:

  • Patient had a short duration of benefit on gefitinib.
  • Patient exhibited a transient response to chemotherapy.
  • Benefit of afatinib post-chemotherapy was surprising to physician, but was welcomed by patient who did not want to receive more chemotherapy.
  • Afatinib was given as a chemotherapy deferral strategy in order to bridge patient to possible immunotherapy.
  • The possibility of the emergence of T790M was discussed during treatment, but repeat biopsies were not routine practice at that time.
  • Patient has been stable for three months after starting nivolumab treatment.

Abbreviations: AE = adverse event; BID = twice daily; CBC = complete blood count; CT = computerized tomography; EGFR = epidermal growth factor receptor; Gy = grays (unit); iv = intravenous; L858R = exon 21 L858R point mutation; M+ = mutation-positive; MRI = magnetic resonance imaging; OD = once daily; PD = progressive disease; PO = per os (by mouth); PR = partial response; q2w = every 2 weeks; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease; T6 = sixth thoracic vertebrae; T790M = exon 20 T790M resistance mutation