Can adding biologic drugs to chemotherapeutic regimes improve cancer outcomes?

The authors reviewed overall survival, progression-free survival and response rate changes with the addition of biologic drugs to chemotherapeutic regimes in metastatic colorectal cancer.

It is estimated that approximately 20-25% of colorectal cancer patients present with distant metastases (spread of cancer to other organs) at diagnosis. Treatment goals for these patients are usually palliative (pain-relieving) rather than curative. However, recent advances in chemotherapy-based regimens have increased overall survival for patients with metastatic colorectal cancer.

Further to this, the addition of biologics (a medicine extracted from biological sources e.g. produced by cell lines) including bevacizumab (Avastin), cetuximab (Erbitux), aflibercept (Zaltrap), panatimumab (Vectibix) and regorafenib (Stivarga), to these regimes have improved outcomes. Biologics are targeted therapies that kill only the cancer cells in the body.

This review provided information on the addition of biologics to some chemotherapeutic regimes.

In a recent phase III trial of addition of bevacizumab to capecitabine in patients above 70 years, addition of bevacizumab was associated with 9.1 months progression-free survival (length of time before advancement of the disease) compared to 5.1 months for capecitabine alone. The response rate (percentage of patients whose cancer shrinks or disappears) was 19.3% when bevacizumab was added to capecitabine compared to 10% when capecitabine was administered alone. Bevacizumab was well tolerated.

In a phase III trial evaluating the addition of bevacizumab to a chemotherapeutic regime of irinotecan, 5-fluorouracil and leucovorin, addition of the biologic was associated with an overall survival of 20.3 months compared to 15.6 months without addition of the biologic. Addition of bevacizumab was associated with a progression-free survival of 10.6 months compared to 6.2 months for the chemotherapeutic regime alone while the response rate was increased from 34.8% to 44.8% with the addition of bevacizumab.

In a study of wild-type (normal) RAS (signaling protein) colorectal cancer, panatimumab plus FOLFOX (a chemotherapy regime consisting of leucovorin, fluorouracil and oxaliplatin) was associated with 26 months overall survival compared to 20.2 months with FOLFOX alone. Similarly, addition of panatimumab to FOLFOX was associated with 10.1 months progression-free survival compared to 7.9 months for FOLFOX alone. However, it was stated that the addition of panatimumab is unlikely to benefit patients with any RAS mutations.

Data on the effectiveness of cetuximab with oxaliplatin-based regimens report conflicting results. A phase II trial demonstrated that adding cetuximab to a FOLFOX regime was associated with 8.3 months progression-free survival compared to 7.2 months for FOLFOX alone. Addition of cetuximab was associated with a 57% response rate compared to 34% when FOLFOX was used alone. However, in a phase III trial comparing the addition of cetuximab to FOLFOX to the use of FOLFOX alone reported no differences in overall survival and progression-free survival. However, the response rate was increased from 58% to 64% with the addition of cetuximab.

In a trial comparing panatimumab plus FOLFOX or bevacizumab plus FOLFOX, patients with wild-type KRAS (signaling protein) receiving panitimumab had a progression-free survival of 13.1 months compared to 9.5 months in those receiving bevacizumab. Overall survival was not reached in the panitimumab arm, while it was 29 months in the bevacizumab arm.

The authors stated that while studies show the benefits of the addition of biologics to a chemotherapeutic regime, the optimum timing of these agents still remains to be defined.