Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non-Small-Cell Lung Cancer: SWOG S0536

Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.

 

This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.


IMGN901 Demonstrates No Significant Benefit, Possible Harm in Small Cell Lung Cancer

The makers of lorvotuzumab mertansine (IMGN901) have halted a clinical trial investigating the use of the drug in extensive-stage small-cell lung cancer (SCLC). An independent monitoring group recommended ending the trial because patients treated with IMGN901 in addition to the chemotherapy agents etoposide (Etopophos) and carboplatin (Paraplatin) fared no better than patients treated with Etopophos and Paraplatin only. Furthermore, the patient group receiving IMGN901 appeared to have higher rates of infections and infection-related deaths, with at least one death potentially related to IMGN901.


Alimta Offers Only Limited Advantage in Lung Cancer Study

The recent PointBreak clinical trial compared two treatment regimens for non-squamous non-small cell lung cancer (NSCLC). Previously untreated patients with advanced non-squamous NSCLC received initial treatment with carboplatin (Paraplatin), bevacizumab (Avastin), and either pemetrexed (Alimta) or paclitaxel (Taxol/Abraxane). The Alimta-treated group was then given maintenance treatment with Alimta and Avastin, while the other patients received Avastin only. Alimta treatment was associated with slightly longer times until the cancer progressed again (average 6.0 months, compared to 5.6 in the Alimta-free regimen). However, overall survival did not differ between the groups. The two regimens differed in what specific side effect were most common, but had similar overall toxicities and were generally tolerable.


PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followe…

PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC).

Overall survival did not improve with the PemCBev regimen compared with the PacCBev regimen, although progression-free survival was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.


New Cancer Drug Reolysin Shrinks Lung Tumors

Interim results from a phase II clinical trial of the new cancer drug Reolysin in squamous cell carcinoma (SCC) of the lung, a type of non-small cell lung cancer (NSCLC), show that tumors shrank in 23 of 25 patients. The patients had SCC that had spread from its original site, or recurred after treatment, and were treated with the chemotherapy drugs Paraplatin (carboplatin) and Taxol/Abraxane (paclitaxel) in addition to Reolysin. Ten patients experienced tumor shrinkage and 13 experienced stable disease, while the cancer progressed in 2 patients. On average, tumors shrank by a third of their original size. Reolysin consists of a modified form of a virus that selectively attacks cancer cells, while producing no symptoms in most healthy people.


Trial of New Lung Cancer Drug OGX-427 Now Enrolling Participants

The Spruce trial, a phase II clinical trial examining the effectiveness of the cancer drug OGX-427 in non-small cell lung cancer (NSCLC), is now open for enrollment. The trial will study patients with previously untreated, advanced non-squamous NSCLC. They will receive the chemotherapy agents carboplatin (Paraplatin) and pemetrexed (Alimta) in combination with either OGX-427 or a placebo. The sponsors also plan to add the Cedar trial, which will investigate the use of OGX-427 in squamous cell NSCLC. OGX-427 inhibits Hsp27, a protein that is highly expressed in many tumor cells. The drug may be especially promising for patients without mutations that make them eligible for currently available targeted therapies.


Chemotherapy-Tarceva Combination May Be Effective for Some Lung Cancer Patients

Results from the FASTACT clinical trial suggest that interspersing erlotinib (Tarceva) among rounds of chemotherapy improves outcomes in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC received six cycles of gemcitabine (Gemzar) plus carboplatin (Paraplatin) or cisplatin (Platinol), with Tarceva added during the second half of each chemotherapy cycle. This regimen prolonged time without cancer worsening and increased survival compared to patients who had received chemotherapy and placebo, though the benefit was only seen in patients with mutations in the EGFR gene. This approach may be most useful for patients whose EGFR status is unknown, as patients with known EGFR mutations may be even better served by first-line treatment with Tarceva alone.


Adding Paraplatin to Alimta Increases Survival in Lung Cancer Study

Results from a phase III clinical trial suggest that adding carboplatin (Paraplatin) to pemetrexed (Alimta) can improve outcomes in non-small cell lung cancer (NSCLC). Over 200 patients with advanced NSCLC received first-line treatment with Alimta either by itself or in combination with Paraplatin. The combination of the two chemotherapy agents extended the time before the cancer started growing again, and prolonged survival compared to Alimta alone. However, the combination treatment group had a higher incidence of serious side effects and four treatment-associated deaths.


Comparison of Combination Chemotherapy Regimens Shows No Significant Differences

Both pemetrexed (Alimta) plus carboplatin (Paraplatin) and Paraplatin plus paclitaxel (Taxol/Abraxane) plus bevacizumab (Avastin) are effective chemotherapy regimens against non-small cell lung cancer (NSCLC). However, until recently, the safety and efficacy of the two regimens had not been directly compared. To evaluate whether one regimen was superior, a phase III clinical trial determined how long patients with advanced non-squamous NSCLC remained free of either cancer progression or severe toxic side effects when treated with either of the two regimens. While patients receiving the Alimta plus Paraplatin regimen tended to have slightly longer relapse- and toxicity-free periods than those given Paraplatin plus Taxol/Abraxane plus Avastin, the difference was not very pronounced and could have happened by chance. The two regimens also did not differ regarding overall time until cancer progression, response rate and overall survival time.