20th Annual Mayo Clinic Hematology/Oncology Reviews

1. What treatment is considered the standard first line treatment for the above patient according to NCCN guidelines:

A. Gemcitabine

B. Gemcitabine and capecitabine

C. Gemcitabine and erlotinib

D. Gemcitabine and cetuxima

E. All of the above

The standard of care for metastatic pancreatic cancer remains single agent gemcitabine. It would be reasonable to consider gemcitabine and capecitabine or gemcitabine and erlotinib as options based on data from randomized trials. Cunningham et al reported in JCO November 22, 2009 on a large phase 3 trial comparing gemcitabine and capecitabine with single agent gemcitabine and found a significant improvement in response rate (19% vs 12%) and PFS (HR 0.78) and a trend towards improvement in overall survival (HR 0.85, p=0.08). They also reported a meta-analysis of 3 randomized trials including their own, showing a statistically significant improvement in overall survival for the combination. In view of these results, they suggest that gemcitabine and capecitabine is one of the new first line treatment options. Given the lack of statistically significant improvement in overall survival from the combination in their trial, one may still consider gemcitabine as standard. A phase 3 trial had also shown that gemcitabine and erlotinib are associated with improvement in overall survival as compared with gemcitabine. A randomized trial of gemcitabine and cetuximab versus gemcitabine showed no improvements in overall survival for the combination. Therefore, B and C would be acceptable answers as well in the appropriate clinical settings. Obviously, all patients should be encouraged to participate in clinical trials.

Explanation

The standard of care for metastatic pancreatic cancer remains single agent gemcitabine. It would be reasonable to consider gemcitabine and capecitabine or gemcitabine and erlotinib as options based on data from randomized trials. Cunningham et al reported in JCO November 22, 2009 on a large phase 3 trial comparing gemcitabine and capecitabine with single agent gemcitabine and found a significant improvement in response rate (19% vs 12%) and PFS (HR 0.78) and a trend towards improvement in overall survival (HR 0.85, p=0.08). They also reported a meta-analysis of 3 randomized trials including their own, showing a statistically significant improvement in overall survival for the combination. In view of these results, they suggest that gemcitabine and capecitabine is one of the new first line treatment options. Given the lack of statistically significant improvement in overall survival from the combination in their trial, one may still consider gemcitabine as standard. A phase 3 trial had also shown that gemcitabine and erlotinib are associated with improvement in overall survival as compared with gemcitabine. A randomized trial of gemcitabine and cetuximab versus gemcitabine showed no improvements in overall survival for the combination. Therefore, B and C would be acceptable answers as well in the appropriate clinical settings. Obviously, all patients should be encouraged to participate in clinical trials.

2. A 45 year old man presents with an absolute eosinophil count of 10,000, congestive heart failure with an echocardiogram showing thickened myocardium consistent with an infiltrating process and bone marrow showing increased atypical eosinophils (40%) and myelofibrosis. Serum troponin levels are elevated and FIP1L1/PDGFRA gene is detected in the peripheral blood. Your treatment recommendation is:

A. Imatinib 400 mg daily

B. Imatinib 100 mg daily

C. Imatinib 400 mg daily and methyl-prednisolone 1 mg/kg daily

D. Alpha interferon therapy

E. Hydroxyurea

HES with FIPL1/PDGFRA gene fusion are highly sensitive to imatinib with nearly 100% response rate. Patients with cardiac involvement are at risk of developing acute necrotizing myocarditis and should be treated with concomitant steroids for 2 weeks.

Explanation

HES with FIPL1/PDGFRA gene fusion are highly sensitive to imatinib with nearly 100% response rate. Patients with cardiac involvement are at risk of developing acute necrotizing myocarditis and should be treated with concomitant steroids for 2 weeks.

3. Your 65 yo male patient with metastatic colon cancer to the liver has responded to 6 cycles of FOLFOX bevacizumab treatment. He has mild neuropathy at this time. He is interested in a break from chemotherapy but is willing to follow your advise. You would recommend:

B. Proceeding with 5FU, leucovorin and bevacizumab would be a reasonable option as per the CONCePT trial

D. None of the above are reasonable recommendations

A 12 month PFS was achieved with 5FU, leucovorin, bevacizumab after initial FOLFOX treatment in CONCePT trial. The arm of discontinuing all chemotherapy in the OPTIMOX2 trial was inferior and cannot be recommended in clinical practice.

Explanation

A 12 month PFS was achieved with 5FU, leucovorin, bevacizumab after initial FOLFOX treatment in CONCePT trial. The arm of discontinuing all chemotherapy in the OPTIMOX2 trial was inferior and cannot be recommended in clinical practice.

4. A 78 year old African American female is diagnosed with stage 4 adenocarcinoma of the lung. She is willing to consider oral treatment that is not associated with alopecia. You have read about the high response rate to erlotinib associated with EGFR activating mutations and would like to know the chances of her having one of these mutations. Based on data from Leidner et al reported in JCO in November 2009, the chances of her tumor harboring one of these mutations is:

A. Very high, 40-60%

B. Very low, 2-4%

C. Intermediate, 20-30%

D. None of the above are correct.

Correct answer is 2%.

Explanation

Correct answer is 2%.

5. The patient obtains a molecular remission with your prescribed treatment. Your recommendation at this time is:

A. To proceed with allogeneic stem cell transplant since it is the only curative treatment.

B. To discontinue treatment and proceed with a course of observation

C. To continue treatment with close follow up.

D. To switch treatment to a non-cross resistant regimen

E. None of the above are correct

Imatinib is highly effective and leads to remissions in most cases. Allogenetic stem cell transplant is the only currently curative treatment but is reserved for patients failing imatinib therapy.

Explanation

Imatinib is highly effective and leads to remissions in most cases. Allogenetic stem cell transplant is the only currently curative treatment but is reserved for patients failing imatinib therapy.

6. A 60 year old female patient is diagnosed with metastatic pancreatic adenocarcinoma to the liver. She is not interested in clinical trail participation. Her performance score is 0 and liver and renal function studies are normal. Based on results of single randomized phase 3 trials, which one(s) of the following regimens have been shown to prolong overall survival compared wit gemcitabine:

A. Gemcitabine and capecitabine

B. Gemcitabine and erlotinib

C. Gemcitabine and cetuximab

D. A and B

E. All of the above

The addition of erlotinib to gemcitabine was associated with an improvement in overall survival in metastatic pancreatic cancer in a phase 3 trial (HR 0.82, p=0.038). None of the other combinations have been associated with improvement in overall survival in a single phase 3 trial. The combination of gemcitabine and capecitabine was reported by Cunningham et al from MRC to have improvement in RR and PFS but the improvement noted in OS did not reach statistical significance. The authors reported a meta-analysis of all reported phase 3 trials and in the meta-analysis, there was a significant improvement in OS noted with the combination.

Explanation

The addition of erlotinib to gemcitabine was associated with an improvement in overall survival in metastatic pancreatic cancer in a phase 3 trial (HR 0.82, p=0.038). None of the other combinations have been associated with improvement in overall survival in a single phase 3 trial. The combination of gemcitabine and capecitabine was reported by Cunningham et al from MRC to have improvement in RR and PFS but the improvement noted in OS did not reach statistical significance. The authors reported a meta-analysis of all reported phase 3 trials and in the meta-analysis, there was a significant improvement in OS noted with the combination.

7. A 58 year old female is diagnosed with a 0.2 cm grade 2 IDC, ER negative, PR negative and HER2 3+ status post lumpectomy. She is wondering if she should receive adjuvant treatment. Based on NCCN guidelines and recommendations of Burstein and Winer in an editorial in JCO December 1, 2009 page 5672, the recommendation should be:

A. No adjuvant systemic treatment

B. A shortened course of chemotherapy and trastuzumab following the FIN-HER regimen

C. Adjuvant chemotherapy with concomitant trastuzumab

D. Adjuvant chemotherapy with sequential trastuzumab

Even though the prognosis of small HER2 tumors (T1a, T1b) seems to be worse than that of HER2 negative tumors, the number of tumors less than 5 mm included in any of the reported series is too small to make any definite conclusions as to whether those patients should be treated or not. In general, chemotherapy and trastuzumab should be strongly considered for T1b or greater tumors.

Explanation

Even though the prognosis of small HER2 tumors (T1a, T1b) seems to be worse than that of HER2 negative tumors, the number of tumors less than 5 mm included in any of the reported series is too small to make any definite conclusions as to whether those patients should be treated or not. In general, chemotherapy and trastuzumab should be strongly considered for T1b or greater tumors.