The ABCs of BAC: Bronchioloalveolar Carcinoma

Transcription

1 The ABCs of BAC: Bronchioloalveolar Carcinoma Howard (Jack) West, MD Medical Oncologist Medical Director, Thoracic Oncology Program Swedish Cancer Institute Seattle, WA March, 2009 President & CEO GRACE Sponsored by the Almquist-Hahn Family The more we learn about healing cancer today, the better the odds that we, and our children, will triumph over this deadly disease tomorrow. For information about sponsoring a presentation about a topic important to you, please info@cancergrace.org

2 Disclaimers The information provided here includes views of the presenter that do not necessarily represent those of the Global Resource for Advancing Cancer Education (GRACE) in general, nor those of Swedish Cancer Institute. The contents of this program do not constitute medical advice and is intended to supplement but not replace input from an individual patient s medical team. BAC: Microscopic & Radiographic View

3 Bronchioloalveolar Carcinoma: General Principles Rising incidence that may account for the increase in adenoca Although pure BAC (WHO criteria) is uncommon (2-4% of cases), BAC component may be present in 15-20% of NSCLC. 1/3 of cases are lifelong non-smokers vs 10% of other NSCLC > 50% of BAC cases are women, vs. <40% of all NSCLC Present with pulmonary infiltrates, sometimes diffuse Generally spreads within lungs >> elsewhere in the body Sometimes copious frothy sputum (brochorrhea) May have better prognosis than other NSCLC, stage for stage Sometimes extremely indolent Some cases progress rapidly Pathologic Subtypes: A Continuum from Pure BAC to Invasive Adenocarcinoma Pure BAC BAC with Invasion Adeno with BAC Adenocarcinoma

4 Improved Survival of Stage I BAC vs. Other Adenocarcinomas 5-year survival 83% vs. 63%, p = 0.04 Breathnach, J Thor Cardiovasc Surg 2001 Improved Survival Also for Advanced BAC vs. Other NSCLC Subtypes Median Surv vs. 9.7 months, p = Breathnach, Cancer 1999

5 BAC Response to Chemotherapy from the Literature BAC rarely assessed carefully, and a percentage of cases in larger trials of advanced NSCLC Some reviews suggest BAC is resistant to chemo, others indicate it s responsive Widely considered to be poorly responsive by oncologists However, BAC lesions are often not amenable to assessment of response by conventional means Feldman Retrospective Review, Mayo Clin Proc 1992 Histology # Resp. Rate BAC 25 32% Non-BAC % BAC Before/After EGFR Inhibitor Gefitinib (Iressa): 5 days between Chest X-Rays Courtesy of Dr. Mark Kris, Memorial Sloan Kettering Cancer Center

6 Prolonged Response to Iressa in BAC November, 2000 December, 2002 Courtesy of Dr. David Gandara, UC-Davis Long-Term Survivors on SWOG 0126, Gefitinib (Iressa) in Advanced BAC N = 135 eligible, N = 16%; median overall survival 13 months No real differences between treatment-naïve and previously treated pts. Significantly better survival among women, never-smokers, patients with rash, and those with PS 0/1 vs. 2 Six patients had progression-free survival beyond four years: Pt Sex Prior Rx? Smoking Status EGFR Mut EGFR FISH Best Resp Yrs. on Rx Current Status A F No Never N/A N/A SD 5.4 Alive, off for SAE B M No Never N/A Pos SD 5.9 Alive, on study C M No Current No Neg SD 4.5 Alive, PD D F No Former No Neg SD 5.6 Alive, on study E F Yes Never N/A N/A SD 4.3 Alive, PD F M No Former Ex. 21 Pos SD 5.0 Alive, on study West, J Clin Oncol 2006; West, Proc ASCO 2008, A#8047

7 MSKCC: Erlotinib (Tarceva) in Advanced BAC, with Molecular Correlates Advanced BAC or adeno/bac, N = 101 Response rate 22%, median OS 17 months If EGFR mutation, RR 83%, median OS 23 months Best responses among patients with EGFR mutations, but many patients did well without one (and some stable disease and minor responses among patients with KRAS mutations) Miller, J Clin Oncol 2008 Phase II Trial of Erlotinib in BAC: Clinical Variables Variable Response Rate Non-Smokers 45% Former/CurrentSmokers 18% Women Men 27% 17% No rash 0% Rash 35% Chemo-naive Prior chemo 21% 35% Pure BAC 11% Adeno/BAC 29%

8 Two Major Subtypes of (Pure) BAC S0126: Overall Survival by Histology (n=65) Previously Untreated Patients 100% BAC Non Mucinous Adeno With BAC BAC Mucinous Invasive Adeno N Events Median in Months NR % P = % 40% 20% 0% Months After Registration Data from Wilbur Franklin, Univ of Colorado

9 Mucinous vs. Non-Mucinous BAC: Clinically Significant Differences? (Preliminary/Limited Data) Thus far, in studies that have looked at BAC subtype, responses to EGFR inhibitors have been seen only in those with nonmucinous BAC EGFR mutations seen in non-mucinous, but not mucinous BAC High proportion of never-smokers much more pronounced in non-mucinous subtype Chemo responsiveness may be more common in mucinous subtype Pneumonic BAC Very diffuse throughout one or more lung lobes Associated with copious, large volume bronchorrhea Often quite resistant to EGFR inhibitors,?chemo as well Thus far, particularly difficult to treat effectively

10 Summary/Conclusions BAC is a unique subtype that accounts for only 2-4% of NSCLC, but it is a component in 15-20% of lung adenocarcinomas Microscope: pure form spreads thinly over air sacs (alveoli) Imaging: diffuse hazy areas (classic description: ground-glass opacity (GGO)) or many small nodules Clinically: many never-smokers, disproportionately female Response to treatment: Some very profound &prolonged responses to oral EGFR inhibitors Patients with EGFR mutations may have the best responses, but others can also do well May be primarily or exclusively in patients with non-mucinous subtype Chemo: often perceived as less beneficial,?due to inability to measure response Pneumonic form appears more resistant BAC is a very new field of research, with much still to learn Questions and Comments? Posts with additional detail on these topics are available at GRACE members can leave comments and questions at