Patient Summary: Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633
The CALGB 9633 trial randomized patients with stage IB non small cell lung cancer NSCLC to either carboplatin/paclitaxel or no further therapy. This study had been stopped early because the investigators saw a significant benefit for the chemotherapy arm. Since then, several other studies have failed to show a benefit for adjuvant chemotherapy (chemo after surgery) in stage IB resected tumors. For this reason, the update of this trial has been much anticipated.
CALGB 9633 randomized patients with completely resected (T2N0M0) NSCLC following surgery to either 4 cycles of carboplatin and paclitaxel or observation alone. The median follow-up at the time of this presentation is 54 months. Unfortunately, the updated analysis no longer demonstrates a significant difference in overall survival between the 2 groups (chemotherapy 63% vs. observation 57.3%, p=0.10 –not significant). A significant overall survival benefit with chemotherapy had been seen at both 2 years (90% vs 84%, p=0.05) and 3 years (79% vs 71%, p=0.043), but did not persist at 5 years (59% vs 57%, p=0.375).
This study correlates with other studies that found no benefit. The advantages in survival at 2 and 3 years and disease free survival (which was improved in the treatment arm: 57.2% vs. 48%, p=0.030) raise the possibility that adjuvant chemotherapy may delay recurrence, even if does not improve long term survival. Further analysis suggests that the benefit of chemotherapy may be limited to patients with tumors >4cm in size, but this requires further study. The results of CALGB 9633 do not mandate the use of adjuvant chemotherapy in patients with stage IB NSCLC.
It is important to note, studies that are reported early (such as the first report of this study) without long term follow up can be misleading. The final conclusion of the study that patients should not receive chemotherapy for early stage lung cancer after surgery (Ib) is exactly the opposite of the preliminary report. Unfortunately, many patients who would not benefit from chemotherapy were offered treatment based on the preliminary data.