Cochrane · intervention · CD010341
Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy
Chan, KKW, Glenny, AM, Weldon, JC, et al. · Cochrane Database of Systematic Reviews · 2015 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
43
current version
GRADE rated
8
No studies
2
Included studies
12
as reported
No studies 2 · 4.7%Ungraded 33 · 76.7%Very low 6 · 14%Low 0 · 0%Moderate 2 · 4.7%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | People diagnosed with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma, histological variants of SCC and carcinoma in situ; head and neck cancer trials included if data available separately or at least 50% of participants had oral cavity or oropharyngeal cancer | Adults with squamous cell carcinoma of the oral cavity or oropharynx; 2488 participants across 12 studies (12% (298) oral cavity, 59% (1468) oropharynx, 29% larynx/hypopharynx, less than 1% other sites) |
| Intervention | Targeted therapy or immunotherapy of the primary tumour as one of the primary interventions, administered concomitantly with standard therapy; any mode of administration; no prior intervention other than diagnostic intervention | EGFR monoclonal antibodies: cetuximab, nimotuzumab (n=1654); Tyrosine kinase inhibitors: erlotinib, gefitinib, lapatinib (n=649); Non-specific immunotherapy: recombinant interleukin-2, BCG cell wall preparation (n=277) |
| Comparison | Standard therapy (chemotherapy, radiotherapy, surgery or a combination) alone | Standard therapy alone: radiotherapy, chemoradiotherapy or surgery (n=1244); placebo plus standard therapy (n=293) |
| Outcomes | Overall survival/total mortality; Locoregional control; Disease-free survival; Progression-free survival or time to recurrence; Harms associated with treatment (adverse events); Quality of life; Direct and indirect costs to participants and health services; Participant satisfaction | Overall survival (n=1421); Locoregional control (n=424); Disease-free survival (n=261); Progression-free survival (n=1315); Adverse events (n=2400); Quality of life (n=424) |
| Study designs | Randomised controlled trials with a minimum follow-up period of six months | Randomised controlled trials, phase I to III (n=12) |
| Timing | Minimum follow-up period of six months | Minimum follow-up of at least 6 months; follow-up 24 to 70 months (monoclonal antibodies and immunotherapy) and 40 to 60 months (tyrosine kinase inhibitors) |
Search date: 2015-02. Databases: Cochrane Oral Health Group's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid; EMBASE via Ovid; US National Institutes of Health Trials Register (clinicaltrials.gov); World Health Organization Clinical Trials Registry Platform; American Society of…
Questions and results
Current version onlyNon-specific immunotherapy (recombinant interleukin-2 or BCG cell wall preparation) plus standard therapy vs Standard therapy alone
Population: People with squamous cell carcinoma of the oral cavity or oropharynx
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Disease-free survival 24 to 70 months · Recombinant interleukin-2 + surgery (De Stefani 2002) | HR 0.66 [0.43, 1.02] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 109 (72 to 163); Moderate-risk 290 (200 to 411);… | 1 study · 201 participants | Very low Downgraded: risk of bias, indirectness |
Adverse effects 24 to 70 months · Nausea/vomiting (rIL-2, grades >=3) | RR 3.40 [0.15, 77.34] | 1 study · 30 participants | Ungraded |
Overall survival 24 to 70 months · BCG cell wall preparation + surgery (Bier 1981) | BCG-CWP + surgery versus surgery alone: 3-year overall survival 10/10 vs 9/10; too few participants to calculate a hazard ratio (Bier 1981, 24 participants). | 1 study · 24 participants | Ungraded |
Adverse effects 24 to 70 months · Moderate to severe chills (BCG-CWP, all grades) | RR 11.00 [0.67, 179.29] | 1 study · 24 participants | Ungraded |
Adverse effects 24 to 70 months · Stomatitis (rIL-2, all grades) | RR 1.47 [0.75, 2.90] | 1 study · 30 participants | Ungraded |
Adverse effects 24 to 70 months · Leukopenia (rIL-2, all grades) | RR 0.57 [0.22, 1.50] | 1 study · 30 participants | Ungraded |
Adverse effects 24 to 70 months · Increased temperature (BCG-CWP, all grades) | RR 0.67 [0.13, 3.30] | 1 study · 24 participants | Ungraded |
Locoregional control 24 to 70 months · Recombinant interleukin-2 + neoadjuvant chemotherapy (Mantovani 1998), tumour response | Response to treatment (Mantovani 1998; neoadjuvant chemotherapy + rIL-2 vs chemotherapy alone): complete response 4/13 vs 3/15; partial response 6/13 vs 9/15. Narrative only; no GRADE rating. | 1 study · 33 participants | Ungraded |
Adverse effects 24 to 70 months · Leukopenia (rIL-2, grades >=3) | RR 0.38 [0.04, 3.26] | 1 study · 30 participants | Ungraded |
Overall survival 24 to 70 months · Recombinant interleukin-2 + surgery (De Stefani 2002) | HR 0.52 [0.31, 0.87] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 87 (53 to 141); Moderate-risk 237 (149 to 363);… | 1 study · 201 participants | Very low Downgraded: risk of bias, indirectness |
Adverse effects 24 to 70 months · Nausea/vomiting (rIL-2, all grades) | RR 1.24 [0.90, 1.70] | 1 study · 30 participants | Ungraded |
Adverse effects 24 to 70 months · Stomatitis (rIL-2, grades >=3) | RR 1.71 [0.33, 8.83] | 1 study · 30 participants | Ungraded |
Adverse effects 24 to 70 months · Gastrointestinal complaints (BCG-CWP, all grades) | RR 5.00 [0.27, 94.34] | 1 study · 24 participants | Ungraded |
EGFR monoclonal antibody (cetuximab or nimotuzumab) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)
Population: People with squamous cell carcinoma of the oral cavity or oropharynx
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 24 to 70 months · Mucositis (all grades) | Mucositis all grades: not estimable due to high heterogeneity (P=0.0009; I2=86%) between subgroups (cetuximab; nimotuzumab) and within cetuximab (I2=93%); 1417 participants, 3 studies. Table 3, row 1.6 (Ang 2014;… | 3 studies · 1417 participants | Ungraded |
Adverse effects 24 to 70 months · Skin toxicity/acneiform rash (cetuximab, all grades) | RR 6.56 [5.35, 8.03] | 2 studies · 1311 participants | Ungraded |
Progression-free survival 24 to 70 months · Monoclonal antibody + chemoradiotherapy vs chemoradiotherapy alone | HR 1.08 [0.89, 1.32] | 1 study · 891 participants | Ungraded |
Participant satisfaction 24 to 70 months | No included studies addressed participant satisfaction (review-wide gap). | 0 studies | No studies |
Overall survival 24 to 70 months | HR 0.82 [0.69, 0.97] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 133 (113 to 156); Moderate-risk 347 (301 to… | 3 studies · 1421 participants | Moderate Downgraded: publication bias |
Progression-free survival 24 to 70 months · Monoclonal antibody + radiotherapy vs radiotherapy alone | HR 0.70 [0.54, 0.91] | 1 study · 424 participants | Ungraded |
Adverse effects 24 to 70 months · Skin toxicity/acneiform rash (nimotuzumab, grades >=3) | RR 0.20 [0.01, 4.05] | 1 study · 92 participants | Ungraded |
Adverse effects 24 to 70 months · Dysphagia (all grades) | RR 0.97 [0.92, 1.03] | 3 studies · 1403 participants | Ungraded |
Direct and indirect costs to participants and health services 24 to 70 months | No included studies addressed direct and indirect costs to participants and health services (review-wide gap). | 0 studies | No studies |
Adverse effects 24 to 70 months · Xerostomia (grades >=3) | RR 1.36 [0.80, 2.31] | 2 studies · 1311 participants | Ungraded |
Adverse effects 24 to 70 months · Skin toxicity/acneiform rash (nimotuzumab, all grades) | RR 1.06 [0.85, 1.31] | 1 study · 92 participants | Ungraded |
Locoregional control 24 to 70 months | HR 0.68 [0.52, 0.89] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 112 (87 to 144); Moderate-risk 297 (237 to 370);… | 1 study · 424 participants | Moderate Downgraded: risk of bias |
Adverse effects 24 to 70 months · Skin toxicity/acneiform rash (cetuximab, grades >=3) | RR 17.72 [8.33, 37.73] | 3 studies · 1403 participants | Ungraded |
Adverse effects 24 to 70 months · Dysphagia (grades >=3) | RR 0.93 [0.83, 1.04] | 3 studies · 1403 participants | Ungraded |
Quality of life 24 to 70 months | Only one study (Bonner 2006, 424 participants) comprehensively assessed quality of life using EORTC QLQ-C30 (v3.0) and QLQ-H&N35; no statistically significant difference between groups for global health status or any… | 1 study · 424 participants | Ungraded |
Adverse effects 24 to 70 months · Mucositis (grades >=3) | RR 1.20 [0.96, 1.51] | 4 studies · 1495 participants | Ungraded |
Adverse effects 24 to 70 months · Xerostomia (all grades) | RR 0.97 [0.91, 1.04] | 3 studies · 1417 participants | Ungraded |
Tyrosine kinase inhibitor (erlotinib, gefitinib or lapatinib) plus standard therapy (radiotherapy or chemoradiotherapy) vs Standard therapy alone (radiotherapy or chemoradiotherapy)
Population: People with squamous cell carcinoma of the oral cavity or oropharynx
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Adverse effects 40 to 60 months · Gastrointestinal complaints (gefitinib, all grades) | RR 1.04 [0.98, 1.11] | 1 study · 226 participants | Ungraded |
Adverse effects 40 to 60 months · Gastrointestinal complaints (lapatinib, all grades) | RR 15.53 [2.18, 110.55] | 1 study · 67 participants | Ungraded |
Adverse effects 40 to 60 months · Skin toxicity (erlotinib, all grades) | RR 6.57 [3.60, 12.00] | 1 study · 191 participants | Ungraded |
Progression-free survival 40 to 60 months | HR 0.80 [0.51, 1.28] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 130 (85 to 200); Moderate-risk 340 (233 to 486);… | 2 studies · 271 participants | Very low Downgraded: risk of bias, imprecision, publication bias |
Adverse effects 40 to 60 months · Skin toxicity (lapatinib, all grades) | RR 2.02 [1.23, 3.32] | 1 study · 67 participants | Ungraded |
Locoregional control 40 to 60 months | HR 0.89 [0.53, 1.49] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 144 (88 to 229); Moderate-risk 370 (241 to 539);… | 2 studies · 271 participants | Very low Downgraded: risk of bias, imprecision, publication bias |
Overall survival 40 to 60 months | HR 0.99 [0.62, 1.57] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 159 (102 to 239); Moderate-risk 402 (275 to… | 2 studies · 271 participants | Very low Downgraded: risk of bias, imprecision, publication bias |
Disease-free survival 40 to 60 months · Gefitinib + radiotherapy (oral cavity) | HR 1.51 [0.61, 3.71] Low-risk 160; Moderate-risk 405; High-risk 650 (per 1000) vs Low-risk 231 (101 to 476); Moderate-risk 543 (271 to… | 1 study · 60 participants | Very low Downgraded: imprecision, indirectness, publication bias |
Adverse effects 40 to 60 months · Mucositis (all grades) | RR 1.03 [0.94, 1.11] | 2 studies · 286 participants | Ungraded |
Adverse effects 40 to 60 months · Mucositis (grades >=3) | RR 1.22 [0.96, 1.56] | 2 studies · 286 participants | Ungraded |
Adverse effects 40 to 60 months · Skin toxicity (gefitinib, all grades) | RR 1.03 [0.82, 1.28] | 2 studies · 286 participants | Ungraded |
Adverse effects 40 to 60 months · Gastrointestinal complaints (grades >=3, pooled) | RR 1.11 [0.83, 1.49] | 3 studies · 484 participants | Ungraded |
Adverse effects 40 to 60 months · Skin toxicity (grades >=3, pooled) | RR 1.25 [0.54, 2.88] | 4 studies · 544 participants | Ungraded |
Molecularly targeted therapy plus standard therapy (chemotherapy and/or radiotherapy and/or surgery) vs Standard therapy alone
Population: Patients with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma and histological variants
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR At least 6 months follow-up | Protocol-planned comparison; no included studies at the protocol stage. | 0 studies | No studies |
Immunotherapy plus standard therapy (chemotherapy and/or radiotherapy and/or surgery) vs Standard therapy alone
Population: Patients with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma and histological variants
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR At least 6 months follow-up | Protocol-planned comparison; no included studies at the protocol stage. | 0 studies | No studies |
Targeted therapy or immunotherapy plus standard therapy vs A different type of targeted therapy or immunotherapy plus standard therapy
Population: Patients with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma and histological variants
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR At least 6 months follow-up | Protocol-planned head-to-head comparison; no included studies at the protocol stage. | 0 studies | No studies |
Targeted therapy or immunotherapy alone vs Placebo
Population: Patients with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma and histological variants
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR At least 6 months follow-up | Protocol anticipated that there would be no studies comparing targeted therapy or immunotherapy alone with placebo. | 0 studies | No studies |
Standard therapy plus targeted therapy vs Standard therapy plus immunotherapy
Population: Patients with cancer of the oral cavity (ICD-O C01-C02, C03, C04, C05-C06) or oropharynx (ICD-O C09, C10); primary squamous cell carcinoma and histological variants
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR At least 6 months follow-up | Protocol anticipated that there would be no studies comparing standard therapy plus targeted therapy with standard therapy plus immunotherapy. | 0 studies | No studies |