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H. Kato
Moderator of
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PL 04 - Closing Plenary: Where We Are Now, and Where We Will Be in 10 Years (ID 587)
- Event: WCLC 2017
- Type: Plenary Session
- Track:
- Presentations: 4
- Moderators:H. Kato, Rafael Rosell
- Coordinates: 10/18/2017, 16:30 - 17:45, Main Hall
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PL 04.01 - Where We Are Now, and Where We Will Be in 10 years: From North American Perspective (ID 7841)
16:30 - 16:50 | Presenting Author(s): Paul A. Bunn, Jr.
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Abstract:
Stage 4 NSCLC 1[st] line Rx: In addition to complete staging, all patients with any histology should have PD-L1 testing of their tumor. In addition patients with an adenocarcinoma histology and never smokers should have molecular testing that would include at least EGFR, ALK, ROS1 and BRAF. If NGS testing is selected that additional genes can be tested including MET,RET, HER2,and NTRK. Patients with a PD-L1 tumor proportion score (TPS) >49% who do not have a molecular driver can be treated with pembrolizumab as their first therapy. This therapy is continued for 2 years or until progression or unacceptable toxicity. For those with a TPS score of 1-49, concurrent chemotherapy plus pembrolizumab may be considered based on the results of a small phase II trial. However, larger phase III trials are in progress and may alter this choice. Patients with a molecular alteration in EGFR, ALK, ROS1, or BRAF are treated with the appropriate TKI or TKI combination in the case of v600E BRAF. Although all of the randomized trials comparing these new therapies to chemotherapy included only PS 0-1 patients, there is clear evidence that patients with PS 2 and even PS 3 and elderly patients may benefit from these therapies and should thus be tested. For patients with a lower TPS score or no molecular abnormality and PS0-1, the standard therapy is a platinum doublet chemotherapy with or without bevacizumab. For patients with adenocarcinoma, the most frequently used regimen is pemetrexed with platinum. In North America the platinum is most often carboplatin because of its preferred toxicity profile. PS 0-1 adenocarcinoma patients may also receive bevacizumab if there are no comorbid conditions that would increase toxicity. A taxane doublet with or without bevacizumab is also acceptable. For patients with squamous carcinoma the platinum doublet usually contains gemcitabine or a taxane with carboplatin with or without bevacizumab. Patients receiving chemotherapy are restaged after 2 cycles. Those with progressive disease are offered second line therapy. Patients with stable disease or response receive 2 additional cycles and are then restaged again. Those with acceptable toxicity and continued response are offered 2 additional cycles for a total of 6. Those without further response or additional toxicity are offered maintenance therapy after the 4 cycles. Patients receiving 6 cycles are also offered maintenance therapy. Maintenance therapy may consist of continued pemetrexed or continued bevacizumab for those responding to these. Switch therapy to pemetrexed or to erlotinib or gemcitabine may be considered. 2[nd] Line Rx. For patients receiving 1[st] line pembrolizumab, 2[nd] line rx is first line chemotherapy as discussed above. For patients progressing on a 1[st] line TKI, the 2[nd] line therapy is most often a 2[nd] or 3[rd] generation TKI. When therapy with a TKI is exhausted, the next line of therapy is standard first line chemotherapy as described above. For patients who receive 1[st] line chemotherapy, the second line therapy is most often immunotherapy which can be any of the 3 approved agents for patients with a TPS score of >1 or nivolumab or atezolizumab for patients with a TPS score of 0. 3[rd] Line Rx: Patients who receive 1[st] line I/O followed by chemo or who receive gene specific TKIs followed by 1[st] line chemotherapy, the 3[rd] line treatment would be what was previously considered 2nl line chemo such as docetaxel +/- ramicirumab. Other chemotherapy agents can also be considered such as gemcitabline, other taxanes or irinotecan. Clinical trials may be substituted for any of these treatments in any lines of therapy. Unresectable Stage III. The standard approach is currently concurrent chemotherapy with chest radiotherapy. This is likely to change as positive results of a trial comparing CT/RT alone to CT/RT followed by immunotherapy with durvalumab were announced in mid-2017. The chest RT is generally about 60 Gy given over 6 weeks. The chemotherapy is generally a platinum doublet with etoposide, paclitaxel or pemetrexed. At the time of progression the algorhythm described for stage 4 above can be instituted. Resectable stage I-IIIA. For stage 1A standard therapy is lobectomy alone or stereotactic body radiotherapy (SBRT) for those who are medically inoperable. Patients with stage IB, especially with poor prognostic features such as large size or vascular invasion may receive neoadjuvant or adjuvant chemotherapy with a cisplatin doublet and surgery is standard while other smaller stage IB tumors are treated with lobectomy alone. Stage II and IIIA patients may be treated with neoadjuvant chemotherapy or neoadjuvant CT/RT followed by surgery. They may also receive surgical resection first followed by adjuvant CT or CT/RT. The future: It is highly likely that immunotherapy combinations will prove to be superior to single checkpoint inhibitors so that the majority of sage IV patients without a molecular driver are likely to receive an immunotherapy combination, likely irrespective of TPS score. For stage IV patients with a molecular driver, it is likely that initial therapy will consist of the TKI plus another agent that can affect the cells that persist after initial TKI therapy. It is likely that immunotherapy combinations and molecular combinations will be used in unresectable stage III disease before, after or during CT/RT and will improve cure rates. I believe that a large change in approach to early stage patients will occur with the development of neoadjuvant immunotherapy and molecular therapy. In these approaches we have the opportunity to improve cure rates as well as to more rapidly develop new therapies based on pathologic complete response rates as we now do in breast cancer. The future is also likely to see new ways to define risk in both smokers and non-smokers so that we can detect patients early and so that we can develop new prevention strategies for those at high risk. Figure 1
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PL 04.02 - Where We Are Now, and Where We Will Be in 10 years: From Asian Perspective (ID 7842)
16:50 - 17:10 | Presenting Author(s): Nagahiro Saijo
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Abstract:
Where we are now, and where we will be in 10 years: From Asian Perspective Nagahiro Saijo, MD, PHD, Tokyo Medical University, Kinki University School Medicine Compared with 30 years ago non-small cell carcinoma(NSCLC) became a vast dominant type of lung cancer and majority of clinical trials focus on it. At the end of 20[th] century, effect of platinum doublet containing third generation cytotoxic drugs reached a plateau and thoracic oncologists felt skepticism to achieve the goal in lung cancer treatment. Development of EGFR-TKIs (Gefitinib and Erlotinib) was one of the biggest breakthroughs for rollback of chemotherapy in lung cancer. The EGFR mutation was discovered in 2004 but it took 5 years until there was general agreement that it was an important driver mutation which could predict for response to EGFR-TKI. Evolution of EGFR-TKI proceeds to irreversible 2[nd] (Afatinib and Dacomitinib) and mutation specific 3[rd] generation (Osimertinib) TKIs which can combat the issues of resistance. In Asia more than 50% of adenocarcinoma are EGFR-Mt+ and physicians experienced many long term survivors like surgical treatment in early stage lung cancer. In addition CTONG trial demonstrated that adjuvant EGFR-TKI (Gefitinib) delays recurrence in EGFR-positive surgically resected EGFR-Mt+ NSCLC. WJOG in Japan is conducting exactly the same schedules of trial. There will be a possibility to conduct study of EGFR-TKI combined with chemoradiotherapy in EGFR-Mｔ+ stage III NSCLC in Asian countries although this strategy was not successful in unselected population. Many driver mutations have been identified and its molecular classification made rapid progress in lung cancer, especially adenocarcinoma. The identification ALK and ROS rearrangement quickly followed by the development of active drugs (Crizotinib, Alectinib, Brigotinib, Lorlatinib ). J-ALEX and ALEX trials clearly showed that Alectinib was extremely active drug against ALK rearranged NSCLC. The Nation Wide Genomic Screening Project (LC-Scrum-Japan) leaded by K Goto has been started on February 2013 in Japan. Under this project many driver mutations have been identified not only in non-squamous cell carcinoma but also in squamous and small cell lung cancer. Many clinical trials are ongoing targeting genomic alterations screened in LC-SCRUM-Japan. Among them LURET trial demonstrated that Vandetanib could show 53% response rate (9/17) in RET+ lung cancer and Crizotinib produced 69% response rate (89/129) in ROS-1+ patients in OxOnc12-01 Asian Global trial. Driver mutation targeted drugs showed dramatic effect compared with standard cytotoxic chemotherapy, however, there is so far no positive data of their combination in spite of clear preclinical synergistic or additive effect. Human RAS oncogenes are the most commonly mutated gene family in Caucasian. About 35% (15% in Asian) of lung cancer are driven by activating mutations of KRAS. RAS is really an oncogenic driver and numerous preclinical studies suggest that KRAS is an excellent and well validated target. However, unlike EGFR, ALK, ROS, there is no effective drugs against KRAS. It will be extremely an important issue to develop KRAS targeting drugs. Robust negative data accumulate in immunotherapy for lung cancer including peptide vaccine therapy. Based on unique idea of Allison J. first immune checkpoint inhibitor, anti-CTLA4 antibody (ipillimumab) produced survival benefit in melanoma. PD-1 was cloned by Honjo T (Japan) on 1992 and antitumor activity of anti-PD-1 antibody was reported on 2002. During past 7 years, immune checkpoint inhibitors have been an exciting new addition to the armamentarium fort lung cancer. Two anti-PD-1 antibodies such as Nivolumab and Pemblolizumab has become a standard for second line treatment of lung cancer based on durable response and marked increase in overall survival. In first line treatment Pemblolizumab prolonged OS and PFS compared with standard chemotherapy in NSCLC with high PD-L1 expression >50% (Keynote024). On the other hand, Nivolumab failed to show PFS benefit compared with cytotoxic agents because of poor patient selection. The most important issue will be how to concentrate responsive population and how to eliminate ineffective patients. Although there is a tendency of correlation between PD-L1 expression and objective response/PFS/OS, responders are experienced even in PD-L1 negative patients. Microsatellite instability has related with response to anti-PD-1 antibody in colorectal cancer. Mutation burden may influence on antigenicity of tumor cells. Infiltration of CD8+ lymphocytes is also considered to be a predictive biomarker but it is too objective for precise quantification. The successful patient selection for immune checkpoint inhibitors may depend on the development of methods for quantitative measurement of tumor specific cytotoxic activity of CD8+ lymphocytes. Can cytotoxic drugs survive as one of the modalities for lung cancer treatment? Combination of cytotoxic drugs and immune checkpoint inhibitors shows promising antitumor activity in lung cancer and gastric cancer. Antibody-drug conjugate (ADC) is a very interesting strategy for effective chemotherapy. DS-8201 targeting HER2, developed by Daiichi-Sankyo showed high response rate and favorable toxicity profile in previously treated HER2 positive gastric and breast cancer. ADC will be a potent strategy in future cytotoxic chemotherapy for lung cancer. Progress in the treatment of small cell lung cancer is very behind because of decrease in absolute number of SCLC patients and no discovery of driver mutations. JCOG conducted serial randomized clinical trials in SCLC. However, treatment result reached a plateau in both of limited and extensive diseases. Discovery of druggable targets in near future may have a significant impact in small cell lung cancer.
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PL 04.03 - Where We Are Now, and Where We Will Be in 10 years: From European Perspective (ID 7843)
17:10 - 17:30 | Presenting Author(s): Giorgio Vittorio Scagliotti
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Abstract not provided
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PL 04.04 - WCLC 2018 - Welcome to Toronto (ID 7844)
17:30 - 17:35 | Presenting Author(s): Andrea Bezjak, Gail Elizabeth Darling, Natasha B Leighl, Frances A Shepherd
- Abstract
- Presentation
Abstract not provided
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