panitumumab
Regulatory sources consulted
Approved indications
- In adults, confirmed RAS wild-type metastatic colorectal cancer: with FOLFOX first-line or as monotherapy after progression on fluoropyrimidine, oxaliplatin, and irinotecan.
- In adults, confirmed KRAS G12C-mutated metastatic colorectal cancer in combination with sotorasib after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based treatment.
Clinical warnings
- Boxed warning · Dermatologic toxicity occurs in about 90% and can be severe, infectious, or fatal. Monitor skin and soft tissues, limit sun exposure, and adjust or discontinue according to severity. — DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2
- Major warning · Do not use as monotherapy or with oxaliplatin-based chemotherapy in RAS-mutant tumors or unknown RAS status, except for the specific KRAS G12C indication with sotorasib; it can increase progression and mortality. — DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2
- Major warning · Monitor magnesium and calcium before, during, and for up to 8 weeks afterward; also correct potassium. Hypomagnesemia can be severe. — DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2
- Major warning · It can cause fatal infusion reactions, acute kidney injury from diarrhea and dehydration, fatal interstitial lung disease, and keratitis or corneal perforation. Withhold or discontinue according to the event. — DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2
- Major warning · The combination with bevacizumab and chemotherapy reduced survival and increased severe toxicity; do not use that combination. — DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2
Drug interactions
- HighBevacizumab with chemotherapy
Mechanism: Adding panitumumab reduced survival and increased Grade 3–5 adverse reactions.
Recommendation: Do not use the combination.
DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0fa4bca-f245-4d92-ae29-b0c630a315c2
- LowSotorasib
Mechanism: It is an approved combination only for confirmed KRAS G12C-mutated metastatic colorectal cancer after appropriate prior therapy.
Recommendation: Give the first sotorasib dose before the first infusion. If sotorasib is temporarily withheld, temporarily withhold panitumumab; if sotorasib is permanently discontinued, permanently discontinue panitumumab.
DailyMed, VECTIBIX set_id e0fa4bca-f245-4d92-ae29-b0c630a315c2https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0fa4bca-f245-4d92-ae29-b0c630a315c2
Adverse events
Common (≥1%)
skin rash · paronychia · fatigue · nausea · diarrhea · stomatitis · hypomagnesemia · pruritus · dry skin
Rare but serious
sepsis or necrotizing fasciitis · fatal infusion reaction · acute kidney injury · fatal interstitial lung disease · ulcerative keratitis or corneal perforation
Pregnancy and lactation
It can cause embryo-fetal harm. Use effective contraception during treatment and for 2 months after the last dose. Do not breastfeed during treatment or for 2 months afterward. It may reversibly reduce female fertility.
Recent literature (PubMed)
KRAS G12C is a mutation that occurs in approximately 3 to 4% of patients with metastatic colorectal cancer. Monotherapy with KRAS G12C inhibitors has yielded only modest efficacy. Combining the KRAS G12C inhibitor sotorasib with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be an effective strategy. In this phase 3, multicenter, open-label, randomized trial, we assigned patients with chemorefractory metastatic colorectal cancer with mutated KRAS G12C who had not received previous treatment with a KRAS G12C inhibitor to receive sotorasib at a dose of 960 mg once daily plus panitumumab (53 patients), sotorasib at a dose of 240 mg once daily plus panitumumab (53 patients), or the investigator's choice of trifluridine-tipiracil or regorafenib (standard care; 54 patients). The primary end point was progression-free survival as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Key secondary end points were overall survival and objective response. After a median follow-up of 7.8 months (range, 0.1 to 13.9), the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 6.3) and 3.9 months (95% CI, 3.7 to 5.8) in the 960-mg sotorasib-panitumumab and 240-mg sotorasib-panitumumab groups, respectively, as compared with 2.2 months (95% CI, 1.9 to 3.9) in the standard-care group. The hazard ratio for disease progression or death in the 960-mg sotorasib-panitumumab group as compared with the standard-care group was 0.49 (95% CI, 0.30 to 0.80; P = 0.006), and the hazard ratio in the 240-mg sotorasib-panitumumab group was 0.58 (95% CI, 0.36 to 0.93; P = 0.03). Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0% (95% CI, 0.0 to 6.6) in the 960-mg sotorasib-panitumumab, 240-mg sotorasib-panitumumab, and standard-care groups, respectively. Treatment-related adverse events of grade 3 or h
Neoadjuvant chemotherapy (NAC) has potential advantages over standard postoperative chemotherapy for locally advanced colon cancer but requires formal evaluation. Patients with radiologically staged T3-4, N0-2, M0 colon cancer were randomly allocated (2:1) to 6 weeks oxaliplatin-fluoropyrimidine preoperatively plus 18 postoperatively (NAC group) or 24 weeks postoperatively (control group). Patients with RAS-wildtype tumors could also be randomly assigned 1:1 to receive panitumumab or not during NAC. The primary end point was residual disease or recurrence within 2 years. Secondary outcomes included surgical morbidity, histopathologic stage, regression grade, completeness of resection, and cause-specific mortality. Log-rank analyses were by intention-to-treat. Of 699 patients allocated to NAC, 674 (96%) started and 606 (87%) completed NAC. In total, 686 of 699 (98.1%) NAC patients and 351 of 354 (99.2%) control patients underwent surgery. Thirty patients (4.3%) allocated to NAC developed obstructive symptoms requiring expedited surgery, but there were fewer serious postoperative complications with NAC than with control. NAC produced marked T and N downstaging and histologic tumor regression (all P < .001). Resection was more often histopathologically complete: 94% (648/686) versus 89% (311/351), P < .001. Fewer NAC than control patients had residual or recurrent disease within 2 years (16.9% [118/699] v 21.5% [76/354]; rate ratio, 0.72 [95% CI, 0.54 to 0.98]; P = .037). Tumor regression correlated strongly with freedom from recurrence. Panitumumab did not enhance the benefit from NAC. Little benefit from NAC was seen in mismatch repair-deficient tumors. Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer can be delivered safely, without increasing perioperative morbidity. This chemotherapy regimen, when given preoperatively, produces marked histopathologic down-staging, fewer incomplete resections, and better 2-year disease c
For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74
Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university's online library. The keywords were "Colorectal Cancer" AND "disease process" OR "disease mechanisms" OR "Current Treatment" OR "Prospects". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoc
In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided P = .20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided P = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.