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V. Hirsh
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ED06 - Symptom Management in Lung Cancer (ID 269)
- Event: WCLC 2016
- Type: Education Session
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:R. Gralla, R. Malayeri
- Coordinates: 12/05/2016, 16:00 - 17:30, Stolz 1
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ED06.03 - Pain Management (ID 6449)
16:30 - 16:45 | Author(s): V. Hirsh
- Abstract
- Presentation
Abstract:
Introduction Pain is the most common symptom in cancer patients and it is also the most common symptom in lung cancer patients.[1]The majority of patients with lung cancer present with advanced stage of the disease at diagnosis. Symptoms may result from local effects of the tumor, from regional or distant spread or from distant effects not related to metastases-paraneoplastic syndromes. Pain in these patients may be associated with depression, fatigue [2] and may affect quality of life and patients’ performance status. Early palliative care including pain management may increase their survival. [3] Pain can be classified by type of pain or according to the origin of the pain. The location or origin of the pain determines the type of pain, thoracic or extrathoracic. Pain Pain is often multifactorial in origin and needs to be addressed in each aspect. It can be acute or chronic. Acute pain can be caused by hemorrhage into a tumor, bone pain secondary to a pathological fracture, visceral pain, ie. from acute intestinal obstruction or perforation of a viscous. Its duration is limited and predictable. Chronic pain is differentiated by its longevity. It is estimated that approximately 75% of cancer patients live with chronic pain. [4] It must be approached with dual aim: relieving the pain as well as preventing further recurrences of pain. Pathophysiology of Pain Physiological pain is termed nociceptive pain due to the stimulation of the sensory nociceptors located in tissues when damaged. They are somatic, visceral, neuropathic and psychogenic pains. [5] Neuropathic pain is associated with a loss of opioid receptors in sensory afferents and an increased release of glutamate in the dorsal horn. The resultant hyperexcitability causes spontaneous pain and hyperalgesia and allodynia in areas adjacent to the nerve damage. There are three main causes of pain in patients with advanced lung cancer: Skeletal metastatic disease 34%, Pancoast tumor 31%, chest wall disease 21%. [6] Principles of Pain Management The World Health Organization analgesic ladder for cancer pain relief provides a stepwise approach to managing pain in cancer patients. [7] Step 1 includes paracetamol or non-steroidal anti-inflammatory drugs. Step 2- weak opioids, ie. codeine. Step 3- strong opioids, ie. morphine. Non-opioid and adjuvant treatments can be added to steps 2 and 3. Different routes of the administration of analgesics and their side effects management will be described. Their advantages and disadvantages of each route of administration will be pointed out. The need of adjuvant treatments such as tricyclic antidepressants and anticonvulsants, corticosteroids, topical analgesics, treatments of nausea, constipation, etc., are an integral part of pain management. Interventional procedures help reduce the doses of analgesics and their side effects. [8] Special mention will be about skeletal metastases and bone targeted agents such as zoledronic acid and denosumab, which have shown ability to reduce the pain and analgesic consumption in lung cancer patients. [9] Complementary therapies which help to control pain will also be mentioned.ie. Acupuncture,[10] psychological methods of care, etc. Conclusion An active multidisciplinary approach is required to manage pain in patients with advanced lung cancer. Multifactorial pain is frequent and may require several different analgesics, along with general palliative care and even special interventional procedures. Patients with advanced lung cancer live longer as there are more treatment options. It is of utmost importance to preserve a good quality of life with a better performance status to enable them to receive now further available therapies. [1] Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. Pain. 1999;82 (32) :263-74. [2] Laird BJ, Scott AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J. Pain Symptom Manage. 2011;42(1): 1-11. [3] Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [4] Ferrell BR, Juarez G. Borneman T. Use of routine and breakthrough analgesia in care. Oncol Nurs Forum. 1999;26(10):1655-61. [5] Portenoy RK, Lesage P. Management of cancer pain. Lancet. 1999;353 (9165):1695-700. [6] Watson PN, Evans RJ. Intractable pain with lung cancer. Pain. 1987; 29(2):163-73. [7] Geneva W. World Health Organisation. Cancer Pain Relief. 1996 [8] Vranken JH, Zuurmond WW, de Lange JJ. Continuous brachial plexus block as treatment for the Pancoast syndrome. Clin J Pain . 2000;16(4):327-33 [9] Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patient with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21(16):3150-7. [10] Cassileth BR, Deng GE, Gomez JE, Johnstone PA, Kumar N, Vickers AJ. Complementary therapies and integrative oncology in lung cancer. ACCP evidence-based clinical practice guidelines (2[nd] edition). Chest. 2007;132(Suppl3):340S-54.
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.05 - First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7 (ID 5347)
15:05 - 15:15 | Author(s): V. Hirsh
- Abstract
- Presentation
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting.
Methods:
LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ~250 PFS events. The primary OS analysis was planned after ~213 OS events and a follow-up period of ≥32 months.
Results:
319 patients were randomised (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.
Conclusion:
Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-023 - Physician Patterns of Care in Patients with EGFR Mutation+ NSCLC: An International Survey into Testing and Treatment Choice (ID 6067)
14:30 - 14:30 | Author(s): V. Hirsh
- Abstract
Background:
(Applied for Late-Breaking Abstract Status) IASLC guidelines recommend EGFR mutation testing should be performed at diagnosis of advanced NSCLC to guide treatment decisions. In 2015 an international survey concluded that not all patients were tested or received test results before treatment initiation. This varied between countries and across regions. The aim of a follow-up survey in 2016 was to assess testing rates and HCP treatment choice in advanced NSCLC to identify improvements and changes compared to 2015.
Methods:
Online survey of 707 oncologists in 11 countries (Canada, China, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, UK, USA) between July - August 2016. China was newly added in 2016. For better comparison with 2015 results, China was excluded from the primary results focus
Results:
Globally*, physicians requested EGFR mutation testing prior to first-line therapy of stage IIIb/IV NSCLC in 80% of patients. However, 18% of ordered tests were not received prior to deciding first-line therapy; an improvement on 2015 with 23%. Excluding histology, the main reasons for not testing prior to first-line therapy were insufficient tissue, poor performance status and long turnaround time. While turnaround time significantly reduced year-on-year (2016: 21% vs. 2015: 30%), globally* 24% of patients receive test results after more than 10 business days. Globally* 79% (2015: 80%) of patients with mutations (M+) were treated with tyrosine kinase inhibitors (TKIs), with large country variations on treatment preference (minimum 68% Germany; maximum 98% Taiwan). Prolonging of survival/extending life (54%*) was deemed the most important therapy goal in first-line treatment. 74%* of physicians stated that a clinically relevant increase in overall survival was the most important treatment attribute when choosing a first-line therapy, closely followed by an increase in progression-free survival (68%) and strong improvement of health related quality of life (66%). Perceived differences between TKIs were reported by 49% of physicians. Further detail will be presented at the congress. *Global figures excluding China
Conclusion:
While year-on-year improvements in EGFR testing rates, and availability of test results prior to first-line therapy are seen, a large proportion of EGFR M+ NSCLC patients are still not receiving targeted treatment with TKIs based on mutation status. Incomplete implementation of guidelines is still observed. The main barriers to testing, including receiving results in time, must be addressed if treatment equality for all eligible patients can be achieved. Physician education and closer guideline concordance are key steps to further improve outcomes.
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P3.02b-044 - Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7 (ID 5327)
14:30 - 14:30 | Author(s): V. Hirsh
- Abstract
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7 trial, afatinib significantly improved median progression-free survival (PFS; HR=0.73 [95% CI, 0.57–0.95], p=0.017), objective response rate (70% vs 56%, p=0.008) and time to treatment failure (TTF; HR=0.73 [95% CI, 0.58–0.92], p=0.007) versus gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated the efficacy and safety of afatinib versus gefitinib in patients aged ≥75 years in a subgroup analysis of LUX-Lung 7 (NCT01466660).
Methods:
Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral afatinib (40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS and adverse events (AEs) by age (≥75/<75 years) were exploratory.
Results:
Of 319 patients randomised in LL7, 40 (13%) were aged ≥75 years (afatinib n=19, gefitinib n=21). Median PFS for both age groups was in line with the overall population and favoured afatinib versus gefitinib (patients ≥75 years: 14.7 vs 10.8 months, HR=0.69 [95% CI, 0.33–1.44]; patients <75 years: 11.0 vs 10.9 months, HR=0.76 [95% CI, 0.58–1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs (all grade [grade 3]) with afatinib in the older patient subgroup were diarrhoea (89% [21%]), rash (63% [5%]), dry skin (37% [0%]), and decreased appetite (32% [0%]). Dose reduction/discontinuation of afatinib due to treatment-related AEs was required in 53%/16% and 40%/5% of the older and younger subgroup, respectively.
Conclusion:
A small subgroup of patients in the LUX-Lung 7 trial were ≥75 years old (13%). In exploratory subgroup analyses of patients aged ≥75 and <75 years old, advancing age did not adversely affect the PFS benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients. These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with EGFRm+ NSCLC.
