Advances in Chemotherapy for Non-Small Cell Lung Cancer

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Allison Lamb
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1 Advances in Chemotherapy for Non-Small Cell Lung Cancer Evan W. Alley, MD, PhD Clinical Associate Professor Abramson Cancer Center at Penn Presbyterian

2 Lung Cancer: Overview Second most common cancer in men and women Accounts for more deaths than breast, colon and prostate cancer combined Research is underfunded Unfavorable stage distribution at the time of diagnosis usually advanced Leading cause of cancer deaths Screening may alter this (low dose spiral CTs detecting lung cancer earlier, when it is more curable) Types of lung cancer: Non small cell lung cancer (NSCLC): 87% Small cell lung cancer (SCLC): 13%

3 What is chemotherapy? Chemotherapy refers to medications that kill living cells Chemotherapy preferentially kills rapidly dividing cells, such as cancer cells. Chemotherapy side effects are often related to damage to normal cells. Normal cells that grow faster are more often affected than slower growing types, such as hair follicles, GI tract, mucous membranes, and bone marrow.

4 When is chemotherapy given? Adjuvant Chemotherapy Neo-Adjuvant Chemotherapy Chemotherapy given after removal of a cancer to help prevent recurrence Chemotherapy given before surgery to help reduce the size of a tumor and prevent recurrence Palliative Chemotherapy Chemotherapy given to control the disease and symptoms, but without the intent to cure

5 What to expect with chemotherapy? Most patients tolerate chemotherapy well. Fatigue is the most common side effect. Excellent medications to control side effects of nausea/vomiting, and low blood counts. Chemotherapy may or may not cause hair loss Taxanes, etoposide: YES Platinums, pemetrexed, gemcitabine: NO Chemotherapy is given intravenously, but doesn t always require a port. Standard treatments are given as an outpatient and may often be given closer to home.

6 Advances in Chemotherapy OLD (pre 1990) 1990) NEWER (post Cisplatin/Carboplatin Paclitaxel Etoposide Docetaxel Vinblastine Gemcitabine Ifosfamide Vinorelbine Mitomycin-C Irinotecan Latest (post 2000) Pemetrexed (non-squamous only) Nanoparticle albumin-bound paclitaxel

7 How much chemotherapy? Adjuvant treatment (after surgery): 4 cycles of platinum-based doublet is standard Cisplatin + pemetrexed Cisplatin + docetaxel Cisplatin + gemcitabine Carboplatin + paclitaxel Locally advanced: definitive chemoradiation Cisplatin/etoposide x 2 cycles (SWOG regimen) Weekly carboplatin/paclitaxel during radiation, plus 2 cycles of full-dose consolidation Cisplatin/pemetrexed x 3 cycles +/- pemetrexed x 4 cycles Carboplatin/pemetrexed x 4 cycles Newest data: immunotherapy with durvalumab after chemo

8 Chemotherapy for Advanced NSCLC Old Standard: 4-6 cycles of platinum-doublet, then observe New chemotherapy when cancer grows Newer Approach: 4-6 cycles of platinum-doublet Maintenance chemotherapy (non-squamous) Pemetrexed Bevacizumab New chemotherapy when cancer grows Newest Approach: Chemo-immunotherapy

9 Anti-Angiogenesis Therapy VEGF-R VEGF Ramucirumab Bevacizumab 1-2 mm Small tumor Larger tumor Nonvascular Dormant Vascular Metastatic potential

10 Anti-Angiogenesis Therapy The addition of VEGF or VEGFR antibodies to chemotherapy improves outcomes BUT, increased risk of bleeding/hemorrhage In the first-line setting for advanced NSCLC 4-6 cycles platinum doublet + bevacizumab (non-squamous only) Bevacizumab maintenance In the second-line or greater Docetaxel + ramucirumab up to 6 cycles Ramucirumab maintenance

11 The Cancer Immunity Cycle: Rational Combinations Anti-CTLA-4 Anti-Angiogenesis Anti-PD1/PD-L1 Chemo / XRT

12 Conclusions Chemotherapy continues to play an important role in the treatment of lung cancer Chemotherapy forms the backbone of treatment Adjuvant chemotherapy improves survival in early stage disease Combination therapy with anti-angiogenic agents can improve outcomes in the advanced setting Rationale combinations of chemotherapy, radiation, immunotherapy (and perhaps anti-angiogenic therapy) can improve response and survival in advanced lung cancer

Medical Treatment of Advanced Lung Cancer

Medical Treatment of Advanced Lung Cancer Oncology for Scientists April 26, 2018 Edwin Yau, MD., Ph.D. Assistant Professor of Oncology Department of Medicine Department of Cancer Genetics and Genomics